3-48573192-G-T

Position:

chr3-48573192-G-T

Variant summary

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

The NM_000094.4(COL7A1):c.6696C>A(p.Pro2232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,614,014 control chromosomes in the GnomAD database, including 295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P2232P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 14 hom., cov: 32)

Exomes 𝑓: 0.018 ( 281 hom. )

Consequence

COL7A1
NM_000094.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: -0.228

Variant links:

Genes affected

COL7A1 (HGNC:2214): (collagen type VII alpha 1 chain) This gene encodes the alpha chain of type VII collagen. The type VII collagen fibril, composed of three identical alpha collagen chains, is restricted to the basement zone beneath stratified squamous epithelia. It functions as an anchoring fibril between the external epithelia and the underlying stroma. Mutations in this gene are associated with all forms of dystrophic epidermolysis bullosa. In the absence of mutations, however, an acquired form of this disease can result from an autoimmune response made to type VII collagen. [provided by RefSeq, Jul 2008]

COL7A1 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=-0.69).

BP6

Variant 3-48573192-G-T is Benign according to our data. Variant chr3-48573192-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 255113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48573192-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.228 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1805/152310) while in subpopulation NFE AF= 0.0195 (1327/68010). AF 95% confidence interval is 0.0186. There are 14 homozygotes in gnomad4. There are 868 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL7A1	NM_000094.4 linkuse as main transcript	c.6696C>A	p.Pro2232=	synonymous_variant	85/119	ENST00000681320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL7A1	ENST00000681320.1 linkuse as main transcript	c.6696C>A	p.Pro2232=	synonymous_variant	85/119		NM_000094.4	P1	Q02388-1
COL7A1	ENST00000328333.12 linkuse as main transcript	c.6696C>A	p.Pro2232=	synonymous_variant	84/118	1		P1	Q02388-1
COL7A1	ENST00000487017.5 linkuse as main transcript	n.2613C>A		non_coding_transcript_exon_variant	50/83	5

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1805

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00889

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.0125

AC:

3128

AN:

250482

Hom.:

AF XY:

0.0130

AC XY:

1757

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.00838

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.00897

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0184

AC:

26913

AN:

1461704

Hom.:

281

Cov.:

AF XY:

0.0182

AC XY:

13223

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.00566

Gnomad4 ASJ exome

AF:

0.00895

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0119

AC:

1805

AN:

152310

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

868

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00320

Gnomad4 AMR

AF:

0.00888

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.0195

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0176

EpiControl

AF:

0.0175

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Epidermolysis bullosa dystrophica

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Uncertain significance, no assertion criteria provided	clinical testing	Natera, Inc.	Jan 17, 2020	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.12

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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