3-48587178-C-T

Position:

• chr3-48587178-C-T

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.3139+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,612,868 control chromosomes in the GnomAD database, including 107,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (18533 hom., cov: 31)
  • Exomes 𝑓: 0.34 (89321 hom.)
• Consequence: COL7A1 NM_000094.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.57

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=-0.91).
• BP6: Variant 3-48587178-C-T is Benign according to our data. Variant chr3-48587178-C-T is described in ClinVar as [Benign]. Clinvar id is 255108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48587178-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL7A1	NM_000094.4	c.3139+12G>A		intron_variant		ENST00000681320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL7A1	ENST00000681320.1	c.3139+12G>A		intron_variant			NM_000094.4	P1
COL7A1	ENST00000328333.12	c.3139+12G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68175 AN: 151740 Hom.: 18494 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.395

GnomAD3 exomes AF: 0.340 AC: 84800 AN: 249290 Hom.: 16838 AF XY: 0.338 AC XY: 45614 AN XY: 134960

Gnomad AFR exome AF: 0.773

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.361

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.326

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.338 AC: 494159 AN: 1461010 Hom.: 89321 Cov.: 71 AF XY: 0.337 AC XY: 245156 AN XY: 726742

Gnomad4 AFR exome AF: 0.786

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.449 AC: 68259 AN: 151858 Hom.: 18533 Cov.: 31 AF XY: 0.447 AC XY: 33178 AN XY: 74206

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.394

Alfa AF: 0.337 Hom.: 12663

Bravo AF: 0.446

Asia WGS AF: 0.318 AC: 1111 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Epidermolysis bullosa dystrophica Benign: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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs2255532; hg19: chr3-48624611; COSMIC: COSV60393071; COSMIC: COSV60393071;