Genetic Variant COL7A1:c.7759-98C>A (chr3-48568632-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000094.4(COL7A1):c.7759-98C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,500,762 control chromosomes in the GnomAD database, including 19,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1494 hom., cov: 33)

Exomes 𝑓: 0.16 ( 18474 hom. )

Consequence

COL7A1
NM_000094.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.442

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-48568632-G-T is Benign according to our data. Variant chr3-48568632-G-T is described in ClinVar as [Benign]. Clinvar id is 1244817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL7A1	NM_000094.4 link	c.7759-98C>A		intron_variant	Intron 104 of 118	ENST00000681320.1	NP_000085.1	Q02388-1Q59F16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1 link	c.7759-98C>A		intron_variant	Intron 104 of 118		NM_000094.4	ENSP00000506558.1		Q02388-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18421

AN:

152162

Hom.:

1495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0342

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.155

GnomAD4 exome

AF:

0.157

AC:

211412

AN:

1348482

Hom.:

18474

Cov.:

AF XY:

0.154

AC XY:

102097

AN XY:

663472

show subpopulations

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.0982

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.000196

Gnomad4 SAS exome

AF:

0.0395

Gnomad4 FIN exome

AF:

0.163

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.121

AC:

18421

AN:

152280

Hom.:

1494

Cov.:

AF XY:

0.117

AC XY:

8713

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0342

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.179

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.149

Hom.:

248

Bravo

AF:

0.116

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.75

DANN

Benign

0.35

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over