rs11643815

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032935.3(MT4):c.143G>A(p.Gly48Asp) variant causes a missense change. The variant allele was found at a frequency of 0.124 in 1,606,480 control chromosomes in the GnomAD database, including 13,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 919 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12600 hom. )

Consequence

MT4
NM_032935.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.09

Publications

20 publications found

Variant links:

Genes affected

MT4 (HGNC:18705): (metallothionein 4) Predicted to enable metal ion binding activity. Predicted to be involved in cellular response to metal ion; cellular zinc ion homeostasis; and detoxification of copper ion. Predicted to act upstream of or within cellular metal ion homeostasis. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MT4 links:

BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

BBS2 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 74
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003320247).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MT4	NM_032935.3 link	c.143G>A	p.Gly48Asp	missense_variant	Exon 3 of 3	ENST00000219162.4	NP_116324.2	P47944

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT4	ENST00000219162.4 link	c.143G>A	p.Gly48Asp	missense_variant	Exon 3 of 3	1	NM_032935.3	ENSP00000219162.3		P47944
BBS2	ENST00000682930.1 link	c.42+1789C>T		intron_variant	Intron 2 of 18			ENSP00000507981.1		A0A804HKL9

Frequencies

GnomAD3 genomes

AF:

0.0979

AC:

14885

AN:

152102

Hom.:

919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.00598

Gnomad SAS

AF:

0.0928

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.0967

GnomAD2 exomes

AF:

0.108

AC:

26310

AN:

244600

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.00576

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.127

AC:

184656

AN:

1454260

Hom.:

12600

Cov.:

AF XY:

0.126

AC XY:

91445

AN XY:

723354

show subpopulations

African (AFR)

AF:

0.0237

AC:

788

AN:

33310

American (AMR)

AF:

0.120

AC:

5246

AN:

43864

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

3477

AN:

25794

East Asian (EAS)

AF:

0.00244

AC:

AN:

39420

South Asian (SAS)

AF:

0.0981

AC:

8355

AN:

85126

European-Finnish (FIN)

AF:

0.103

AC:

5500

AN:

53224

Middle Eastern (MID)

AF:

0.102

AC:

585

AN:

5732

European-Non Finnish (NFE)

AF:

0.139

AC:

153921

AN:

1107734

Other (OTH)

AF:

0.111

AC:

6688

AN:

60056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

7742

15483

23225

30966

38708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5442

10884

16326

21768

27210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0978

AC:

14881

AN:

152220

Hom.:

919

Cov.:

AF XY:

0.0950

AC XY:

7071

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0289

AC:

1201

AN:

41538

American (AMR)

AF:

0.100

AC:

1532

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

501

AN:

3472

East Asian (EAS)

AF:

0.00599

AC:

AN:

5176

South Asian (SAS)

AF:

0.0929

AC:

448

AN:

4824

European-Finnish (FIN)

AF:

0.100

AC:

1060

AN:

10602

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9647

AN:

67996

Other (OTH)

AF:

0.0952

AC:

201

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

676

1351

2027

2702

3378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.116

Hom.:

2884

Bravo

AF:

0.0932

TwinsUK

AF:

0.146

AC:

541

ALSPAC

AF:

0.137

AC:

528

ESP6500AA

AF:

0.0292

AC:

128

ESP6500EA

AF:

0.132

AC:

1135

ExAC

AF:

0.109

AC:

13240

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.3

PhyloP100

6.1

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.33

Sift

Benign

0.13

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.32

MPC

0.16

ClinPred

0.024

GERP RS

5.9

Varity_R

0.69

gMVP

0.28

Mutation Taster

=35/65

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over