chr10-104048170-T-C

Variant names:

• chr10-104048170-T-C
• rs79924817
• NM_000494.4:c.2228-66A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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:33679): (microRNA 936) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000494.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	NM_000494.4	MANE Select	c.2228-66A>G		intron	N/A	NP_000485.3
	MIR936	NR_030760.1		n.17A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL17A1	ENST00000648076.2	MANE Select	c.2228-66A>G		intron	N/A	ENSP00000497653.1
	MIR936	ENST00000401264.1	TSL:6	n.17A>G		non_coding_transcript_exon	Exon 1 of 1
	COL17A1	ENST00000369733.8	TSL:5	c.2228-66A>G		intron	N/A	ENSP00000358748.3

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

GnomAD2 exomes AF: 0.00181 AC: 454 AN: 251276 AF XY: 0.00127

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 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

African (AFR) AF: 0.0167 AC: 544 AN: 32508

American (AMR) AF: 0.00351 AC: 157 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.000194 AC: 5 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.0000820 AC: 7 AN: 85384

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53402

Middle Eastern (MID) AF: 0.00759 AC: 43 AN: 5664

European-Non Finnish (NFE) AF: 0.000397 AC: 424 AN: 1067046

Other (OTH) AF: 0.00245 AC: 144 AN: 58700

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

African (AFR) AF: 0.0179 AC: 744 AN: 41552

American (AMR) AF: 0.00601 AC: 92 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68024

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.43
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

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: rs79924817; hg19: chr10-105807928;