rs79924817

Positions:

• chr10-104048170-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000494.4(COL17A1):​c.2228-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,564,964 control chromosomes in the GnomAD database, including 17 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 0.0058 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (9 hom.)
• Consequence: COL17A1 NM_000494.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

Genes affected

COL17A1 (HGNC:2194): (collagen type XVII alpha 1 chain) This gene encodes the alpha chain of type XVII collagen. Unlike most collagens, collagen XVII is a transmembrane protein. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes at the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Mutations in this gene are associated with both generalized atrophic benign and junctional epidermolysis bullosa. Two homotrimeric forms of type XVII collagen exist. The full length form is the transmembrane protein. A soluble form, referred to as either ectodomain or LAD-1, is generated by proteolytic processing of the full length form. [provided by RefSeq, Jul 2008]

MIR936 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00584 (890/152296) while in subpopulation AFR AF= 0.0179 (744/41552). AF 95% confidence interval is 0.0168. There are 8 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL17A1	NM_000494.4	c.2228-66A>G		intron_variant		ENST00000648076.2	NP_000485.3
MIR936	NR_030760.1	n.17A>G		non_coding_transcript_exon_variant	1/1
MIR936	unassigned_transcript_1783	n.3A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL17A1	ENST00000648076.2	c.2228-66A>G		intron_variant			NM_000494.4	ENSP00000497653.1
COL17A1	ENST00000369733.8	c.2228-66A>G		intron_variant		5		ENSP00000358748.3
MIR936	ENST00000401264.1	n.17A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.00580 AC: 883 AN: 152178 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00181 AC: 454 AN: 251276 Hom.: 6 AF XY: 0.00127 AC XY: 173 AN XY: 135808

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000555

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.000939 AC: 1326 AN: 1412668 Hom.: 9 Cov.: 25 AF XY: 0.000840 AC XY: 593 AN XY: 705888

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.000194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000820

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000397

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.00584 AC: 890 AN: 152296 Hom.: 8 Cov.: 32 AF XY: 0.00552 AC XY: 411 AN XY: 74478

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00378 Hom.: 0

Bravo AF: 0.00702

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs79924817; hg19: chr10-105807928;