rs79924817

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.189

Publications

5 publications found

Variant links:

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]

COL17A1 links:

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]

MIR936 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COL17A1	NM_000494.4 link	c.2228-66A>G	intron_variant	Intron 29 of 55	ENST00000648076.2	NP_000485.3
MIR936	NR_030760.1 link	n.17A>G	non_coding_transcript_exon_variant	Exon 1 of 1
MIR936	unassigned_transcript_1783	n.3A>G	non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COL17A1	ENST00000648076.2 link	c.2228-66A>G	intron_variant	Intron 29 of 55		NM_000494.4	ENSP00000497653.1
MIR936	ENST00000401264.1 link	n.17A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
COL17A1	ENST00000369733.8 link	c.2228-66A>G	intron_variant	Intron 28 of 50	5		ENSP00000358748.3

Frequencies

GnomAD3 genomes

AF:

0.00580

AC:

883

AN:

152178

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.000840

AC XY:

593

AN XY:

705888

show subpopulations

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:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39470

South Asian (SAS)

AF:

0.0000820

AC:

AN:

85384

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00759

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.000397

AC:

424

AN:

1067046

Other (OTH)

AF:

0.00245

AC:

144

AN:

58700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

149

224

298

373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00584

AC:

890

AN:

152296

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0179

AC:

744

AN:

41552

American (AMR)

AF:

0.00601

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68024

Other (OTH)

AF:

0.00569

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00378

Hom.:

Bravo

AF:

0.00702

Asia WGS

AF:

0.00115

AC:

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

(source)

DANN

Benign

0.43

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over