3-48564190-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000094.4(COL7A1):c.*216G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00714 in 645,270 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (24 hom.)
• Consequence: COL7A1 NM_000094.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.107

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-48564190-C-G is Benign according to our data. Variant chr3-48564190-C-G is described in ClinVar as [Benign]. Clinvar id is 903070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00596 (908/152364) while in subpopulation NFE AF= 0.00969 (659/68030). AF 95% confidence interval is 0.00907. There are 7 homozygotes in gnomad4. There are 426 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL7A1	NM_000094.4	c.*216G>C		3_prime_UTR_variant	119/119	ENST00000681320.1
COL7A1	XM_017005688.2	c.*216G>C		3_prime_UTR_variant	118/118

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL7A1	ENST00000681320.1	c.*216G>C		3_prime_UTR_variant	119/119		NM_000094.4	P1

Frequencies

GnomAD3 genomes AF: 0.00598 AC: 910 AN: 152246 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00969

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00751 AC: 3702 AN: 492906 Hom.: 24 Cov.: 5 AF XY: 0.00736 AC XY: 1918 AN XY: 260548

Gnomad4 AFR exome AF: 0.00136

Gnomad4 AMR exome AF: 0.00269

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0000326

Gnomad4 SAS exome AF: 0.00371

Gnomad4 FIN exome AF: 0.00601

Gnomad4 NFE exome AF: 0.00968

Gnomad4 OTH exome AF: 0.00635

GnomAD4 genome AF: 0.00596 AC: 908 AN: 152364 Hom.: 7 Cov.: 32 AF XY: 0.00572 AC XY: 426 AN XY: 74508

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00411

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.00969

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00471 Hom.: 1

Bravo AF: 0.00528

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epidermolysis bullosa dystrophica Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	13
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1803298; hg19: chr3-48601623;