Genetic Variant COL6A6:p.Ser21Ser (chr3-130560427-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001102608.3(COL6A6):c.63C>T(p.Ser21Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 1,607,194 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0076 ( 69 hom. )

Consequence

COL6A6
NM_001102608.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0001597

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.304

Variant links:

Genes affected

COL6A6 (HGNC:27023): (collagen type VI alpha 6 chain) This gene encodes a large protein that contains multiple von Willebrand factor domains and forms a component of the basal lamina of epithelial cells. This protein may regulate epithelial cell-fibronectin interactions. Variation in this gene may be implicated in skin diseases. [provided by RefSeq, May 2017]

COL6A6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-130560427-C-T is Benign according to our data. Variant chr3-130560427-C-T is described in ClinVar as [Benign]. Clinvar id is 773137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.304 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1976/152108) while in subpopulation AFR AF= 0.0318 (1319/41468). AF 95% confidence interval is 0.0304. There are 37 homozygotes in gnomad4. There are 890 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A6	NM_001102608.3 link	c.63C>T	p.Ser21Ser	splice_region_variant, synonymous_variant	Exon 2 of 37	ENST00000358511.11	NP_001096078.1	A6NMZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A6	ENST00000358511.11 link	c.63C>T	p.Ser21Ser	splice_region_variant, synonymous_variant	Exon 2 of 37	5	NM_001102608.3	ENSP00000351310.6		A6NMZ7-1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1974

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0319

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00678

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00646

AC:

1592

AN:

246270

Hom.:

AF XY:

0.00564

AC XY:

753

AN XY:

133578

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.00558

Gnomad ASJ exome

AF:

0.00859

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000503

Gnomad FIN exome

AF:

0.000749

Gnomad NFE exome

AF:

0.00680

Gnomad OTH exome

AF:

0.00688

GnomAD4 exome

AF:

0.00757

AC:

11020

AN:

1455086

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

5267

AN XY:

723756

show subpopulations

Gnomad4 AFR exome

AF:

0.0305

Gnomad4 AMR exome

AF:

0.00595

Gnomad4 ASJ exome

AF:

0.00968

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000576

Gnomad4 FIN exome

AF:

0.000886

Gnomad4 NFE exome

AF:

0.00806

Gnomad4 OTH exome

AF:

0.00720

GnomAD4 genome

AF:

0.0130

AC:

1976

AN:

152108

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

890

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0318

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00680

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00803

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00173

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.088

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over