17-19915288-A-G

Variant names:

• chr17-19915288-A-G
• rs119672
• NM_007202.4:c.1834+4748T>C

Variant summary

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

The NM_007202.4(AKAP10):​c.1834+4748T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,030 control chromosomes in the GnomAD database, including 14,386 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 0.42 (14386 hom., cov: 32)
• Consequence: AKAP10 NM_007202.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 11 publications found

Genes affected

AKAP10 (HGNC:368): (A-kinase anchoring protein 10) This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP10	NM_007202.4	c.1834+4748T>C		intron_variant	Intron 12 of 14	ENST00000225737.11	NP_009133.2
AKAP10	NM_001330152.2	c.1660+4748T>C		intron_variant	Intron 11 of 13		NP_001317081.1
AKAP10	XR_007065258.1	n.1873+4748T>C		intron_variant	Intron 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP10	ENST00000225737.11	c.1834+4748T>C		intron_variant	Intron 12 of 14	1	NM_007202.4	ENSP00000225737.6
AKAP10	ENST00000395536.7	c.1660+4748T>C		intron_variant	Intron 11 of 13	5		ENSP00000378907.3
AKAP10	ENST00000583951.1	c.145+4748T>C		intron_variant	Intron 2 of 3	3		ENSP00000463398.1
AKAP10	ENST00000578898.1	n.*167+4748T>C		intron_variant	Intron 3 of 5	3		ENSP00000466329.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64328 AN: 151914 Hom.: 14363 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.424 AC: 64403 AN: 152030 Hom.: 14386 Cov.: 32 AF XY: 0.420 AC XY: 31238 AN XY: 74330

African (AFR) AF: 0.570 AC: 23617 AN: 41446

American (AMR) AF: 0.430 AC: 6569 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.189 AC: 979 AN: 5174

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4822

European-Finnish (FIN) AF: 0.347 AC: 3670 AN: 10566

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25583 AN: 67962

Other (OTH) AF: 0.412 AC: 870 AN: 2110

Alfa AF: 0.411 Hom.: 2327

Bravo AF: 0.439

Asia WGS AF: 0.238 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.81
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs119672; hg19: chr17-19818601;