rs713431

Positions:

• chr17-40981793-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KRT40	NM_001389244.1	c.687+514C>T		intron_variant		ENST00000377755.9
LOC107985072	XR_001752886.2	n.348-535G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT40	ENST00000377755.9	c.687+514C>T		intron_variant		1	NM_001389244.1	P1
KRT40	ENST00000398486.2	c.687+514C>T		intron_variant		1		P1
KRT40	ENST00000684280.1	c.687+514C>T		intron_variant				P1
KRT40	ENST00000461923.5	c.688-469C>T		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.136

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

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

LitVar

Other links and lift over

dbSNP: rs713431; hg19: chr17-39138045;