3-48568632-G-T

Variant names:

• chr3-48568632-G-T
• rs2532848
• NM_000094.4:c.7759-98C>A

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.7759-98C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,500,762 control chromosomes in the GnomAD database, including 19,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1494 hom., cov: 33)
  • Exomes 𝑓: 0.16 (18474 hom.)
• Consequence: COL7A1 NM_000094.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.442
• Publications: 6 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=-0.83).
• BP6: Variant 3-48568632-G-T is Benign according to our data. Variant chr3-48568632-G-T is described in ClinVar as Benign. ClinVar VariationId is 1244817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL7A1	NM_000094.4	c.7759-98C>A		intron_variant	Intron 104 of 118	ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1	c.7759-98C>A		intron_variant	Intron 104 of 118		NM_000094.4	ENSP00000506558.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18421 AN: 152162 Hom.: 1495 Cov.: 33

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.157 AC: 211412 AN: 1348482 Hom.: 18474 Cov.: 24 AF XY: 0.154 AC XY: 102097 AN XY: 663472

African (AFR) AF: 0.0288 AC: 890 AN: 30940

American (AMR) AF: 0.0982 AC: 3512 AN: 35756

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2840 AN: 23826

East Asian (EAS) AF: 0.000196 AC: 7 AN: 35664

South Asian (SAS) AF: 0.0395 AC: 3060 AN: 77504

European-Finnish (FIN) AF: 0.163 AC: 7917 AN: 48508

Middle Eastern (MID) AF: 0.0961 AC: 521 AN: 5422

European-Non Finnish (NFE) AF: 0.178 AC: 184634 AN: 1034810

Other (OTH) AF: 0.143 AC: 8031 AN: 56052

GnomAD4 genome AF: 0.121 AC: 18421 AN: 152280 Hom.: 1494 Cov.: 33 AF XY: 0.117 AC XY: 8713 AN XY: 74450

African (AFR) AF: 0.0342 AC: 1420 AN: 41564

American (AMR) AF: 0.128 AC: 1957 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0308 AC: 149 AN: 4830

European-Finnish (FIN) AF: 0.166 AC: 1758 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12183 AN: 68002

Other (OTH) AF: 0.154 AC: 325 AN: 2116

Alfa AF: 0.162 Hom.: 775

Bravo AF: 0.116

Asia WGS AF: 0.0230 AC: 79 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	-0.83
CADD	Benign	0.75
DANN	Benign	0.35
PhyloP100		-0.44
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: rs2532848; hg19: chr3-48606065;