dbSNP rs7290488: C1QTNF6:p.Gly55Asp (chr22-37185343-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_031910.4(C1QTNF6):c.164G>A(p.Gly55Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,360 control chromosomes in the GnomAD database, including 23,076 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G55S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.13 ( 1563 hom., cov: 31)

Exomes 𝑓: 0.16 ( 21513 hom. )

Consequence

C1QTNF6
NM_031910.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.330

Publications

21 publications found

Variant links:

Genes affected

C1QTNF6 (HGNC:14343): (C1q and TNF related 6) Predicted to enable identical protein binding activity. Predicted to be located in extracellular space. Predicted to be integral component of membrane. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF6 links:

IL2RB-AS1 (HGNC:40300):

IL2RB-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=0.0018802285).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF6	NM_031910.4 link	c.164G>A	p.Gly55Asp	missense_variant	Exon 2 of 3	ENST00000337843.7	NP_114116.3	Q9BXI9-2A0A024R1J0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF6	ENST00000337843.7 link	c.164G>A	p.Gly55Asp	missense_variant	Exon 2 of 3	1	NM_031910.4	ENSP00000338812.2		Q9BXI9-2

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19988

AN:

152054

Hom.:

1564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0475

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.144

GnomAD2 exomes

AF:

0.123

AC:

30808

AN:

249906

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.0777

Gnomad AMR exome

AF:

0.0885

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.000273

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.164

AC:

239572

AN:

1461188

Hom.:

21513

Cov.:

AF XY:

0.161

AC XY:

116904

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.0682

AC:

2282

AN:

33470

American (AMR)

AF:

0.0928

AC:

4148

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4313

AN:

26116

East Asian (EAS)

AF:

0.000328

AC:

AN:

39670

South Asian (SAS)

AF:

0.0506

AC:

4360

AN:

86196

European-Finnish (FIN)

AF:

0.126

AC:

6693

AN:

53208

Middle Eastern (MID)

AF:

0.0971

AC:

560

AN:

5768

European-Non Finnish (NFE)

AF:

0.187

AC:

208025

AN:

1111706

Other (OTH)

AF:

0.152

AC:

9178

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11427

22855

34282

45710

57137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7162

14324

21486

28648

35810

<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:

0.131

AC:

19992

AN:

152172

Hom.:

1563

Cov.:

AF XY:

0.126

AC XY:

9361

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0787

AC:

3267

AN:

41518

American (AMR)

AF:

0.127

AC:

1935

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

539

AN:

3466

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0474

AC:

228

AN:

4814

European-Finnish (FIN)

AF:

0.126

AC:

1337

AN:

10610

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12248

AN:

67972

Other (OTH)

AF:

0.143

AC:

302

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

869

1739

2608

3478

4347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.157

Hom.:

4312

Bravo

AF:

0.130

TwinsUK

AF:

0.201

AC:

747

ALSPAC

AF:

0.198

AC:

762

ESP6500AA

AF:

0.0833

AC:

367

ESP6500EA

AF:

0.177

AC:

1518

ExAC

AF:

0.122

AC:

14785

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.3

(source)

DANN

Benign

0.95

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.10

.;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

0.33

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.44

N;N;D

REVEL

Benign

0.044

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.22

T;T;D

Vest4

0.20

MPC

0.46

ClinPred

0.0037

GERP RS

1.1

Varity_R

0.037

gMVP

0.46

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

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