rs721411

Variant names:

• chr17-41492692-C-T
• rs721411
• ENST00000393986.2:c.-359G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393986.2(KRT36):​c.-359G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 247,412 control chromosomes in the GnomAD database, including 1,345 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 0.087 (834 hom., cov: 32)
  • Exomes 𝑓: 0.078 (511 hom.)
• Consequence: KRT36 ENST00000393986.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• Publications: 5 publications found

Genes affected

KRT36 (HGNC:6454): (keratin 36) The protein encoded by this gene is a member of the keratin gene family. This type I hair keratin is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT36	ENST00000393986.2	c.-359G>A		upstream_gene_variant		1		ENSP00000377555.2

Frequencies

GnomAD3 genomes AF: 0.0869 AC: 13212 AN: 152058 Hom.: 831 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.0497

Gnomad OTH AF: 0.0907

GnomAD4 exome AF: 0.0779 AC: 7421 AN: 95234 Hom.: 511 AF XY: 0.0829 AC XY: 4151 AN XY: 50102

African (AFR) AF: 0.0968 AC: 356 AN: 3678

American (AMR) AF: 0.223 AC: 1269 AN: 5698

Ashkenazi Jewish (ASJ) AF: 0.0382 AC: 86 AN: 2252

East Asian (EAS) AF: 0.216 AC: 1171 AN: 5418

South Asian (SAS) AF: 0.114 AC: 1639 AN: 14420

European-Finnish (FIN) AF: 0.0414 AC: 170 AN: 4106

Middle Eastern (MID) AF: 0.0691 AC: 26 AN: 376

European-Non Finnish (NFE) AF: 0.0445 AC: 2415 AN: 54280

Other (OTH) AF: 0.0577 AC: 289 AN: 5006

GnomAD4 genome AF: 0.0870 AC: 13236 AN: 152178 Hom.: 834 Cov.: 32 AF XY: 0.0900 AC XY: 6695 AN XY: 74404

African (AFR) AF: 0.108 AC: 4485 AN: 41526

American (AMR) AF: 0.170 AC: 2592 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1148 AN: 5164

South Asian (SAS) AF: 0.150 AC: 723 AN: 4808

European-Finnish (FIN) AF: 0.0473 AC: 501 AN: 10592

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0497 AC: 3382 AN: 68010

Other (OTH) AF: 0.0898 AC: 190 AN: 2116

Alfa AF: 0.0706 Hom.: 340

Bravo AF: 0.101

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.43
PhyloP100		0.27
PromoterAI		0.13	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs721411; hg19: chr17-39648944;