rs2555364

Positions:

• chr15-48127189-C-G

Variant summary

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

The NM_205850.3(SLC24A5):​c.301+5153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,138 control chromosomes in the GnomAD database, including 54,371 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 0.81 (54371 hom., cov: 32)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

Genes affected

SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A5	NM_205850.3	c.301+5153C>G		intron_variant		ENST00000341459.8
SLC24A5	XM_047432394.1	c.301+5153C>G		intron_variant
SLC24A5	XM_024449901.2			upstream_gene_variant
SLC24A5	XM_047432395.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A5	ENST00000341459.8	c.301+5153C>G		intron_variant		1	NM_205850.3	P1
SLC24A5	ENST00000449382.2	c.121+6024C>G		intron_variant		1
SLC24A5	ENST00000463289.1	n.61+5153C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122968 AN: 152020 Hom.: 54373 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.808 AC: 122997 AN: 152138 Hom.: 54371 Cov.: 32 AF XY: 0.808 AC XY: 60068 AN XY: 74382

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.841

Alfa AF: 0.896 Hom.: 7955

Bravo AF: 0.779

Asia WGS AF: 0.601 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.57

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: rs2555364; hg19: chr15-48419386;