rs9878950

Variant names:

• chr3-48571073-T-C
• rs9878950
• NM_000094.4:c.7164+28A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• epidermolysis bullosa with congenital localized absence of skin and deformity of nails

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• dystrophic epidermolysis bullosa pruriginosa

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
• recessive dystrophic epidermolysis bullosa

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Genomics England PanelApp, Ambry Genetics, G2P, ClinGen
• generalized dominant dystrophic epidermolysis bullosa

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet
• pretibial dystrophic epidermolysis bullosa

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• transient bullous dermolysis of the newborn

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• acral dystrophic epidermolysis bullosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dystrophic epidermolysis bullosa, nails only

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• recessive dystrophic epidermolysis bullosa inversa

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• recessive dystrophic epidermolysis bullosa-generalized other

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1223033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL7A1	NM_000094.4	c.7164+28A>G		intron_variant	Intron 94 of 118	ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1	c.7164+28A>G		intron_variant	Intron 94 of 118		NM_000094.4	ENSP00000506558.1

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

GnomAD2 exomes AF: 0.0701 AC: 17483 AN: 249294 AF XY: 0.0631

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 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

African (AFR) AF: 0.408 AC: 13655 AN: 33472

American (AMR) AF: 0.0544 AC: 2432 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2854 AN: 26130

East Asian (EAS) AF: 0.0916 AC: 3636 AN: 39698

South Asian (SAS) AF: 0.0462 AC: 3984 AN: 86246

European-Finnish (FIN) AF: 0.0399 AC: 2126 AN: 53234

Middle Eastern (MID) AF: 0.138 AC: 795 AN: 5766

European-Non Finnish (NFE) AF: 0.0312 AC: 34637 AN: 1111270

Other (OTH) AF: 0.0773 AC: 4664 AN: 60348

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

African (AFR) AF: 0.386 AC: 15989 AN: 41444

American (AMR) AF: 0.0826 AC: 1263 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3468

East Asian (EAS) AF: 0.110 AC: 564 AN: 5148

South Asian (SAS) AF: 0.0482 AC: 232 AN: 4810

European-Finnish (FIN) AF: 0.0400 AC: 424 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0341 AC: 2319 AN: 67988

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.0654 Hom.: 1905

Bravo AF: 0.156

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.30
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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