Variant rs2233971 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014070.3(C6orf15):c.10C>T(p.Arg4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000531 in 1,545,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

C6orf15
NM_014070.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

C6orf15 (HGNC:13927): (chromosome 6 open reading frame 15) Predicted to enable several functions, including collagen V binding activity; fibronectin binding activity; and glycosaminoglycan binding activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in interstitial matrix. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

C6orf15 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029039323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6orf15	NM_014070.3 linkuse as main transcript	c.10C>T	p.Arg4Cys	missense_variant	1/2	ENST00000259870.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6orf15	ENST00000259870.4 linkuse as main transcript	c.10C>T	p.Arg4Cys	missense_variant	1/2	1	NM_014070.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000795

AC:

AN:

150860

Hom.:

AF XY:

0.0000755

AC XY:

AN XY:

79464

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000468

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000546

AC:

AN:

1393080

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

686920

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.000376

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000504

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.1

DANN

Benign

0.96

DEOGEN2

Benign

0.022

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0050

M_CAP

Benign

0.0054

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.043

Sift

Benign

0.22

Sift4G

Benign

0.18

Polyphen

0.012

Vest4

0.047

MutPred

0.34

Loss of methylation at R4 (P = 0.0168);

MVP

0.12

MPC

1.0

ClinPred

0.11

GERP RS

-2.4

Varity_R

0.057

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over