rs6760875

Positions:

• chr2-228061182-A-G

Variant summary

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

The NM_001142644.2(SPHKAP):​c.247-33639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,138 control chromosomes in the GnomAD database, including 34,524 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 0.67 (34524 hom., cov: 33)
• Consequence: SPHKAP NM_001142644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

Genes affected

SPHKAP (HGNC:30619): (SPHK1 interactor, AKAP domain containing) Enables protein kinase A binding activity. Predicted to be located in Z disc. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPHKAP	NM_001142644.2	c.247-33639T>C		intron_variant		ENST00000392056.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPHKAP	ENST00000392056.8	c.247-33639T>C		intron_variant		1	NM_001142644.2	P2
SPHKAP	ENST00000344657.5	c.247-33639T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101883 AN: 152020 Hom.: 34465 Cov.: 33

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.671 AC: 102010 AN: 152138 Hom.: 34524 Cov.: 33 AF XY: 0.673 AC XY: 50095 AN XY: 74388

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.673

Alfa AF: 0.613 Hom.: 58008

Bravo AF: 0.675

Asia WGS AF: 0.729 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs6760875; hg19: chr2-228925898;