rs11827029

Positions:

• chr11-62488145-C-T

Variant summary

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

The ENST00000257247.11(AHNAK):​c.442+3587G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,206 control chromosomes in the GnomAD database, including 3,927 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 (3927 hom., cov: 32)
• Consequence: AHNAK ENST00000257247.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHNAK	NM_024060.4	c.442+3587G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHNAK	ENST00000257247.11	c.442+3587G>A		intron_variant		1		P1
AHNAK	ENST00000530124.5	c.342+46858G>A		intron_variant		3
AHNAK	ENST00000525875.1	n.448+3587G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22000 AN: 152088 Hom.: 3911 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.145 AC: 22058 AN: 152206 Hom.: 3927 Cov.: 32 AF XY: 0.141 AC XY: 10526 AN XY: 74434

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0956 Hom.: 278

Bravo AF: 0.159

Asia WGS AF: 0.0660 AC: 229 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	1.8
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11827029; hg19: chr11-62255617;