rs713431

Variant names:

• chr17-40981793-G-A
• rs713431
• NM_001389244.1:c.687+514C>T

Variant summary

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

The NM_001389244.1(KRT40):​c.687+514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,184 control chromosomes in the GnomAD database, including 1,395 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 0.13 (1395 hom., cov: 32)
• Consequence: KRT40 NM_001389244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• 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]

LOC107985072 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT40	NM_001389244.1	c.687+514C>T		intron_variant	Intron 3 of 6	ENST00000377755.9	NP_001376173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT40	ENST00000377755.9	c.687+514C>T		intron_variant	Intron 3 of 6	1	NM_001389244.1	ENSP00000366984.4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19981 AN: 152066 Hom.: 1396 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.131 AC: 19991 AN: 152184 Hom.: 1395 Cov.: 32 AF XY: 0.134 AC XY: 9973 AN XY: 74408

African (AFR) AF: 0.156 AC: 6466 AN: 41508

American (AMR) AF: 0.169 AC: 2591 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3468

East Asian (EAS) AF: 0.157 AC: 812 AN: 5182

South Asian (SAS) AF: 0.177 AC: 852 AN: 4816

European-Finnish (FIN) AF: 0.143 AC: 1513 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7047 AN: 68000

Other (OTH) AF: 0.136 AC: 287 AN: 2114

Alfa AF: 0.115 Hom.: 126

Bravo AF: 0.136

Asia WGS AF: 0.176 AC: 612 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	5.2
DANN	Benign	0.69
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs713431; hg19: chr17-39138045;