rs2513046

Positions:

• chr11-62468622-A-G
• chr11-62468622-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024060.4(AHNAK):​c.442+23110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,062 control chromosomes in the GnomAD database, including 57,967 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 0.87 (57967 hom., cov: 29)
• Consequence: AHNAK NM_024060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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]

AHNAK (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHNAK	NM_024060.4	c.442+23110T>C		intron_variant			NP_076965.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000257247.11	c.442+23110T>C		intron_variant		1		ENSP00000257247.7
AHNAK	ENST00000530124.5	c.343-34731T>C		intron_variant		3		ENSP00000433789.1
AHNAK	ENST00000525875.1	n.448+23110T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132242 AN: 151944 Hom.: 57929 Cov.: 29

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.870 AC: 132328 AN: 152062 Hom.: 57967 Cov.: 29 AF XY: 0.872 AC XY: 64783 AN XY: 74334

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.843

Alfa AF: 0.902 Hom.: 28391

Bravo AF: 0.852

Asia WGS AF: 0.861 AC: 2997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2513046; hg19: chr11-62236094;