rs972249

Variant names:

• chr17-40986715-A-G
• rs972249
• ENST00000398486.2:c.-73+332T>C

Variant summary

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

The ENST00000398486.2(KRT40):​c.-73+332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,124 control chromosomes in the GnomAD database, including 30,996 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 0.62 (30996 hom., cov: 28)
• Consequence: KRT40 ENST00000398486.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 1 publications found

Genes affected

KRT40 (HGNC:26707): (keratin 40) This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2009]

ENSG00000306126 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT40	NM_001385217.1	c.-73+207T>C		intron_variant	Intron 1 of 8		NP_001372146.1
KRT40	NM_182497.4	c.-73+332T>C		intron_variant	Intron 1 of 8		NP_872303.2
KRT40	NR_163403.1	n.80+207T>C		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT40	ENST00000398486.2	c.-73+332T>C		intron_variant	Intron 1 of 8	1		ENSP00000381500.2
KRT40	ENST00000684280.1	c.-73+207T>C		intron_variant	Intron 1 of 8			ENSP00000506768.1
KRT40	ENST00000461923.5	n.-73+207T>C		intron_variant	Intron 1 of 8	2		ENSP00000434458.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94282 AN: 151014 Hom.: 30958 Cov.: 28

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.618

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.624 AC: 94367 AN: 151124 Hom.: 30996 Cov.: 28 AF XY: 0.623 AC XY: 45969 AN XY: 73750

African (AFR) AF: 0.840 AC: 34556 AN: 41134

American (AMR) AF: 0.601 AC: 9150 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3118 AN: 5126

South Asian (SAS) AF: 0.662 AC: 3173 AN: 4794

European-Finnish (FIN) AF: 0.489 AC: 5026 AN: 10284

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35589 AN: 67796

Other (OTH) AF: 0.614 AC: 1294 AN: 2108

Alfa AF: 0.557 Hom.: 39133

Bravo AF: 0.648

Asia WGS AF: 0.659 AC: 2293 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.073
DANN	Benign	0.24
PhyloP100		-2.0
PromoterAI		0.054	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs972249; hg19: chr17-39142967; COSMIC: COSV66697166; COSMIC: COSV66697166;