15-48126448-A-G

Position:

• chr15-48126448-A-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+4412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,166 control chromosomes in the GnomAD database, including 7,856 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 0.20 (7856 hom., cov: 32)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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]

SLC24A5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.301+4412A>G		intron_variant		ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.301+4412A>G		intron_variant			XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.301+4412A>G		intron_variant		1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.121+5283A>G		intron_variant		1		ENSP00000389966.2
SLC24A5	ENST00000463289.1	n.61+4412A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30312 AN: 152048 Hom.: 7826 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00788

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.200 AC: 30403 AN: 152166 Hom.: 7856 Cov.: 32 AF XY: 0.200 AC XY: 14899 AN XY: 74406

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.00631

Gnomad4 NFE AF: 0.00788

Gnomad4 OTH AF: 0.170

Alfa AF: 0.0685 Hom.: 830

Bravo AF: 0.229

Asia WGS AF: 0.403 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.56

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: rs2675347; hg19: chr15-48418645;