Variant 3-48573492-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000094.4(COL7A1):c.6618+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,613,920 control chromosomes in the GnomAD database, including 2,461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 441 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2020 hom. )

Consequence

COL7A1
NM_000094.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0650

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-48573492-T-C is Benign according to our data. Variant chr3-48573492-T-C is described in ClinVar as [Benign]. Clinvar id is 1265238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL7A1	NM_000094.4 linkuse as main transcript	c.6618+21A>G		intron_variant		ENST00000681320.1	NP_000085.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
COL7A1	ENST00000681320.1 linkuse as main transcript	c.6618+21A>G	intron_variant		NM_000094.4	ENSP00000506558	P1	Q02388-1
COL7A1	ENST00000328333.12 linkuse as main transcript	c.6618+21A>G	intron_variant	1		ENSP00000332371	P1	Q02388-1
COL7A1	ENST00000487017.5 linkuse as main transcript	n.2535+21A>G	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0674

AC:

10251

AN:

152064

Hom.:

434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0497

Gnomad AMR

AF:

0.0427

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0486

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0679

GnomAD3 exomes

AF:

0.0584

AC:

14664

AN:

251300

Hom.:

582

AF XY:

0.0560

AC XY:

7607

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.0398

Gnomad ASJ exome

AF:

0.0801

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.0465

Gnomad FIN exome

AF:

0.0477

Gnomad NFE exome

AF:

0.0447

Gnomad OTH exome

AF:

0.0528

GnomAD4 exome

AF:

0.0484

AC:

70803

AN:

1461738

Hom.:

2020

Cov.:

AF XY:

0.0484

AC XY:

35192

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.0409

Gnomad4 ASJ exome

AF:

0.0766

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.0458

Gnomad4 FIN exome

AF:

0.0496

Gnomad4 NFE exome

AF:

0.0431

Gnomad4 OTH exome

AF:

0.0606

GnomAD4 genome

AF:

0.0676

AC:

10289

AN:

152182

Hom.:

441

Cov.:

AF XY:

0.0668

AC XY:

4970

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0425

Gnomad4 ASJ

AF:

0.0827

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0489

Gnomad4 FIN

AF:

0.0505

Gnomad4 NFE

AF:

0.0456

Gnomad4 OTH

AF:

0.0738

Alfa

AF:

0.0490

Hom.:

324

Bravo

AF:

0.0686

Asia WGS

AF:

0.145

AC:

506

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.7

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over