rs9878950

chr3-48571073-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000094.4(COL7A1):c.7164+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 1,612,936 control chromosomes in the GnomAD database, including 7,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (3367 hom., cov: 32)
  • Exomes 𝑓: 0.047 (4301 hom.)
• Consequence: COL7A1 NM_000094.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-48571073-T-C is Benign according to our data. Variant chr3-48571073-T-C is described in ClinVar as [Benign]. Clinvar id is 1223033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL7A1	NM_000094.4	c.7164+28A>G		intron_variant		ENST00000681320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL7A1	ENST00000681320.1	c.7164+28A>G		intron_variant			NM_000094.4	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21466 AN: 151938 Hom.: 3347 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.0701 AC: 17483 AN: 249294 Hom.: 1538 AF XY: 0.0631 AC XY: 8551 AN XY: 135424

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.0503

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.0468

Gnomad FIN exome AF: 0.0388

Gnomad NFE exome AF: 0.0349

Gnomad OTH exome AF: 0.0675

GnomAD4 exome AF: 0.0471 AC: 68783 AN: 1460880 Hom.: 4301 Cov.: 33 AF XY: 0.0461 AC XY: 33520 AN XY: 726780

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.0544

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0916

Gnomad4 SAS exome AF: 0.0462

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0312

Gnomad4 OTH exome AF: 0.0773

GnomAD4 genome AF: 0.142 AC: 21535 AN: 152056 Hom.: 3367 Cov.: 32 AF XY: 0.140 AC XY: 10389 AN XY: 74328

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.0826

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0671 Hom.: 646

Bravo AF: 0.156

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.57
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs9878950; hg19: chr3-48608506; COSMIC: COSV60393008; COSMIC: COSV60393008;