rs2428549

Positions:

• chr11-62544922-A-G

Variant summary

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

The NM_001620.3(AHNAK):​c.-100+1738T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,050 control chromosomes in the GnomAD database, including 7,857 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 0.31 (7857 hom., cov: 32)
• Consequence: AHNAK NM_001620.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHNAK	NM_001620.3	c.-100+1738T>C		intron_variant		ENST00000378024.9	NP_001611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000378024.9	c.-100+1738T>C		intron_variant		2	NM_001620.3	ENSP00000367263

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47535 AN: 151932 Hom.: 7851 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.313 AC: 47575 AN: 152050 Hom.: 7857 Cov.: 32 AF XY: 0.304 AC XY: 22570 AN XY: 74344

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.332

Alfa AF: 0.342 Hom.: 1165

Bravo AF: 0.311

Asia WGS AF: 0.139 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.3
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2428549; hg19: chr11-62312394;