chr3-48573957-G-A

Variant names:

• chr3-48573957-G-A
• rs9871180
• NM_000094.4:c.6502-67C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 rank	MANE	Protein	UniProt
COL7A1	NM_000094.4	c.6502-67C>T		intron_variant	Intron 80 of 118	ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1	c.6502-67C>T		intron_variant	Intron 80 of 118		NM_000094.4	ENSP00000506558.1
COL7A1	ENST00000328333.12	c.6502-67C>T		intron_variant	Intron 79 of 117	1		ENSP00000332371.8
COL7A1	ENST00000487017.5	n.2419-67C>T		intron_variant	Intron 45 of 82	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

African (AFR) AF: 0.0686 AC: 2253 AN: 32858

American (AMR) AF: 0.0267 AC: 1125 AN: 42210

Ashkenazi Jewish (ASJ) AF: 0.0708 AC: 1824 AN: 25756

East Asian (EAS) AF: 0.0862 AC: 3359 AN: 38968

South Asian (SAS) AF: 0.0420 AC: 3542 AN: 84352

European-Finnish (FIN) AF: 0.0415 AC: 2182 AN: 52526

Middle Eastern (MID) AF: 0.0491 AC: 205 AN: 4174

European-Non Finnish (NFE) AF: 0.0289 AC: 31799 AN: 1099800

Other (OTH) AF: 0.0444 AC: 2639 AN: 59432

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

African (AFR) AF: 0.0662 AC: 2747 AN: 41486

American (AMR) AF: 0.0314 AC: 480 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 254 AN: 3466

East Asian (EAS) AF: 0.102 AC: 529 AN: 5166

South Asian (SAS) AF: 0.0445 AC: 214 AN: 4808

European-Finnish (FIN) AF: 0.0408 AC: 432 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0317 AC: 2154 AN: 67998

Other (OTH) AF: 0.0522 AC: 110 AN: 2108

Alfa AF: 0.0331 Hom.: 47

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
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9871180; hg19: chr3-48611390;