rs11231111

Positions:

• chr11-62492533-C-T

Variant summary

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

The NM_024060.4(AHNAK):​c.343-702G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,948 control chromosomes in the GnomAD database, including 3,536 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 0.14 (3536 hom., cov: 31)
• Consequence: AHNAK NM_024060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHNAK	NM_024060.4	c.343-702G>A		intron_variant			NP_076965.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000257247.11	c.343-702G>A		intron_variant		1		ENSP00000257247.7
AHNAK	ENST00000530124.5	c.342+42470G>A		intron_variant		3		ENSP00000433789.1
AHNAK	ENST00000533365.5	c.343-702G>A		intron_variant		5		ENSP00000433635.1
AHNAK	ENST00000525875.1	n.349-702G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21012 AN: 151832 Hom.: 3521 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.139 AC: 21066 AN: 151948 Hom.: 3536 Cov.: 31 AF XY: 0.136 AC XY: 10067 AN XY: 74286

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0823 Hom.: 417

Bravo AF: 0.152

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.84
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11231111; hg19: chr11-62260005;