rs2433354

Positions:

• chr15-48122772-C-T

Variant summary

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

The NM_205850.3(SLC24A5):​c.301+736C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,144 control chromosomes in the GnomAD database, including 7,788 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 (7788 hom., cov: 32)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.301+736C>T		intron_variant		ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.301+736C>T		intron_variant			XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.301+736C>T		intron_variant		1	NM_205850.3	ENSP00000341550	P1
SLC24A5	ENST00000449382.2	c.121+1607C>T		intron_variant		1		ENSP00000389966
SLC24A5	ENST00000482911.2	c.*668C>T		3_prime_UTR_variant	2/2	2		ENSP00000453395
SLC24A5	ENST00000463289.1	n.61+736C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29709 AN: 151974 Hom.: 7757 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.0192 AC: 1 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.196 AC: 29801 AN: 152092 Hom.: 7788 Cov.: 32 AF XY: 0.196 AC XY: 14612 AN XY: 74376

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.163

Alfa AF: 0.0470 Hom.: 1761

Bravo AF: 0.226

Asia WGS AF: 0.399 AC: 1380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.23

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: rs2433354; hg19: chr15-48414969;