rs9881877

Positions:

• chr3-48575963-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000094.4(COL7A1):​c.5821-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,612,342 control chromosomes in the GnomAD database, including 7,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (3493 hom., cov: 33)
  • Exomes 𝑓: 0.048 (4422 hom.)
• Consequence: COL7A1 NM_000094.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0410

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-48575963-G-A is Benign according to our data. Variant chr3-48575963-G-A is described in ClinVar as [Benign]. Clinvar id is 1229441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL7A1	NM_000094.4	c.5821-61C>T		intron_variant		ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1	c.5821-61C>T		intron_variant			NM_000094.4	ENSP00000506558	P1
COL7A1	ENST00000328333.12	c.5821-61C>T		intron_variant		1		ENSP00000332371	P1
COL7A1	ENST00000487017.5	n.1738-61C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21853 AN: 152034 Hom.: 3473 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.0476 AC: 69575 AN: 1460190 Hom.: 4422 AF XY: 0.0467 AC XY: 33932 AN XY: 726462

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.0558

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0911

Gnomad4 SAS exome AF: 0.0465

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.144 AC: 21921 AN: 152152 Hom.: 3493 Cov.: 33 AF XY: 0.142 AC XY: 10569 AN XY: 74394

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.140

Alfa AF: 0.102 Hom.: 351

Bravo AF: 0.159

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Epidermolysis bullosa dystrophica Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs9881877; hg19: chr3-48613396; COSMIC: COSV60393058; COSMIC: COSV60393058;