11-62438816-C-T

Variant names:

• chr11-62438816-C-T
• rs9645690
• ENST00000257247.11:c.443-4925G>A

Variant summary

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

The ENST00000257247.11(AHNAK):​c.443-4925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,992 control chromosomes in the GnomAD database, including 9,740 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 0.34 (9740 hom., cov: 31)
• Consequence: AHNAK ENST00000257247.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 5 publications found

Genes affected

AHNAK (HGNC:347): (AHNAK nucleoprotein) The protein encoded by this gene is a large (700 kDa) structural scaffold protein consisting of a central domain with 128 aa repeats. The encoded protein may play a role in such diverse processes as blood-brain barrier formation, cell structure and migration, cardiac calcium channel regulation, and tumor metastasis. A much shorter variant encoding a 17 kDa isoform exists for this gene, and the shorter isoform initiates a feedback loop that regulates alternative splicing of this gene. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHNAK	NM_024060.4	c.443-4925G>A		intron_variant	Intron 5 of 5		NP_076965.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000257247.11	c.443-4925G>A		intron_variant	Intron 5 of 5	1		ENSP00000257247.7
AHNAK	ENST00000530124.5	c.343-4925G>A		intron_variant	Intron 2 of 2	3		ENSP00000433789.1
AHNAK	ENST00000525875.1	n.449-4925G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51154 AN: 151874 Hom.: 9730 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.337 AC: 51177 AN: 151992 Hom.: 9740 Cov.: 31 AF XY: 0.346 AC XY: 25719 AN XY: 74286

African (AFR) AF: 0.201 AC: 8337 AN: 41464

American (AMR) AF: 0.495 AC: 7553 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3379 AN: 5160

South Asian (SAS) AF: 0.599 AC: 2882 AN: 4812

European-Finnish (FIN) AF: 0.327 AC: 3455 AN: 10562

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23034 AN: 67952

Other (OTH) AF: 0.348 AC: 733 AN: 2104

Alfa AF: 0.343 Hom.: 29502

Bravo AF: 0.341

Asia WGS AF: 0.577 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		-0.13
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: rs9645690; hg19: chr11-62206288;