3-48573957-G-A

Position:

• chr3-48573957-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000094.4(COL7A1):​c.6502-67C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,592,188 control chromosomes in the GnomAD database, including 1,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (191 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1045 hom.)
• Consequence: COL7A1 NM_000094.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL7A1	NM_000094.4	c.6502-67C>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.6502-67C>T		intron_variant			NM_000094.4	ENSP00000506558	P1
COL7A1	ENST00000328333.12	c.6502-67C>T		intron_variant		1		ENSP00000332371	P1
COL7A1	ENST00000487017.5	n.2419-67C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6957 AN: 151994 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0499

GnomAD4 exome AF: 0.0340 AC: 48928 AN: 1440076 Hom.: 1045 AF XY: 0.0341 AC XY: 24444 AN XY: 715864

Gnomad4 AFR exome AF: 0.0686

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.0708

Gnomad4 EAS exome AF: 0.0862

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0415

Gnomad4 NFE exome AF: 0.0289

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0458 AC: 6968 AN: 152112 Hom.: 191 Cov.: 32 AF XY: 0.0460 AC XY: 3418 AN XY: 74360

Gnomad4 AFR AF: 0.0662

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0733

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0445

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0173 Hom.: 6

Bravo AF: 0.0449

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
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: rs9871180; hg19: chr3-48611390;