chr3-48573957-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000094.4(COL7A1):​c.6502-67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,440,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1440170 Hom.: 0 AF XY: 0.00000140 AC XY: 1 AN XY: 715916

African (AFR) AF: 0.00 AC: 0 AN: 32858

American (AMR) AF: 0.0000711 AC: 3 AN: 42218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25758

East Asian (EAS) AF: 0.00 AC: 0 AN: 38970

South Asian (SAS) AF: 0.00 AC: 0 AN: 84360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4174

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099872

Other (OTH) AF: 0.00 AC: 0 AN: 59432

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 47

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		-0.55

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;