dbSNP rs2242655: C6orf47:p.Lys92Asn (chr6-31659672-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021184.4(C6orf47):c.276G>C(p.Lys92Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,968 control chromosomes in the GnomAD database, including 17,000 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 0.14 ( 1740 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15260 hom. )

Consequence

C6orf47
NM_021184.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.451

Publications

41 publications found

Variant links:

Genes affected

C6orf47 (HGNC:19076): (chromosome 6 open reading frame 47)

C6orf47 links:

C6orf47-AS1 (HGNC:39767): (C6orf47 antisense RNA 1)

C6orf47-AS1 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=0.0035974681).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf47	NM_021184.4 link	c.276G>C	p.Lys92Asn	missense_variant	Exon 1 of 1	ENST00000375911.2	NP_067007.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6orf47	ENST00000375911.2 link	c.276G>C	p.Lys92Asn	missense_variant	Exon 1 of 1	6	NM_021184.4	ENSP00000365076.1		O95873
C6orf47-AS1	ENST00000422049.1 link	n.352-728C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20589

AN:

152122

Hom.:

1736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.152

AC:

37393

AN:

246464

AF XY:

0.145

show subpopulations

Gnomad AFR exome

AF:

0.0811

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.0290

Gnomad EAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.135

AC:

197583

AN:

1460728

Hom.:

15260

Cov.:

AF XY:

0.133

AC XY:

96501

AN XY:

726678

show subpopulations

African (AFR)

AF:

0.0693

AC:

2320

AN:

33480

American (AMR)

AF:

0.224

AC:

10000

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

805

AN:

26136

East Asian (EAS)

AF:

0.215

AC:

8520

AN:

39700

South Asian (SAS)

AF:

0.101

AC:

8718

AN:

86258

European-Finnish (FIN)

AF:

0.310

AC:

16213

AN:

52288

Middle Eastern (MID)

AF:

0.0531

AC:

306

AN:

5768

European-Non Finnish (NFE)

AF:

0.129

AC:

143325

AN:

1111988

Other (OTH)

AF:

0.122

AC:

7376

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12401

24802

37203

49604

62005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5192

10384

15576

20768

25960

<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:

0.135

AC:

20612

AN:

152240

Hom.:

1740

Cov.:

AF XY:

0.144

AC XY:

10698

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0806

AC:

3351

AN:

41560

American (AMR)

AF:

0.189

AC:

2892

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3472

East Asian (EAS)

AF:

0.147

AC:

762

AN:

5182

South Asian (SAS)

AF:

0.104

AC:

503

AN:

4830

European-Finnish (FIN)

AF:

0.329

AC:

3484

AN:

10580

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9154

AN:

68000

Other (OTH)

AF:

0.106

AC:

224

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

928

1856

2785

3713

4641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.121

Hom.:

950

Bravo

AF:

0.125

TwinsUK

AF:

0.129

AC:

479

ALSPAC

AF:

0.124

AC:

478

ESP6500AA

AF:

0.0851

AC:

257

ESP6500EA

AF:

0.134

AC:

724

ExAC

AF:

0.146

AC:

17102

Asia WGS

AF:

0.141

AC:

491

AN:

3478

EpiCase

AF:

0.113

EpiControl

AF:

0.115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

0.45

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.060

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.018

Polyphen

0.98

Vest4

0.030

MutPred

0.14

Loss of ubiquitination at K92 (P = 0.0047);

MPC

0.78

ClinPred

0.015

GERP RS

3.5

Varity_R

0.095

gMVP

0.035

Mutation Taster

=100/0

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

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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