chr11-62492533-C-T

Variant names:

• chr11-62492533-C-T
• rs11231111
• ENST00000257247.11:c.343-702G>A

Variant summary

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

The ENST00000257247.11(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 ENST00000257247.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 1 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=-0.93).
• 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 rank	MANE	Protein	UniProt
AHNAK	NM_024060.4	c.343-702G>A		intron_variant	Intron 4 of 5		NP_076965.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000257247.11	c.343-702G>A		intron_variant	Intron 4 of 5	1		ENSP00000257247.7
AHNAK	ENST00000530124.5	c.342+42470G>A		intron_variant	Intron 2 of 2	3		ENSP00000433789.1
AHNAK	ENST00000533365.5	c.343-702G>A		intron_variant	Intron 4 of 4	5		ENSP00000433635.1
AHNAK	ENST00000525875.1	n.349-702G>A		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.401 AC: 16581 AN: 41308

American (AMR) AF: 0.0707 AC: 1080 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3468

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5174

South Asian (SAS) AF: 0.0317 AC: 153 AN: 4820

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0346 AC: 2354 AN: 67986

Other (OTH) AF: 0.120 AC: 253 AN: 2106

Alfa AF: 0.0837 Hom.: 664

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
PhyloP100		-0.24
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: rs11231111; hg19: chr11-62260005;