rs4775737

Positions:

• chr15-48129132-G-A

Variant summary

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

The NM_205850.3(SLC24A5):​c.302-5126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 151,994 control chromosomes in the GnomAD database, including 194 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 0.032 (194 hom., cov: 32)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.302-5126G>A		intron_variant		ENST00000341459.8	NP_995322.1
SLC24A5	XM_024449901.2	c.-39+1719G>A		intron_variant			XP_024305669.2
SLC24A5	XM_047432394.1	c.302-5126G>A		intron_variant			XP_047288350.1
SLC24A5	XM_047432395.1	c.-39+569G>A		intron_variant			XP_047288351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.302-5126G>A		intron_variant		1	NM_205850.3	ENSP00000341550	P1
SLC24A5	ENST00000449382.2	c.122-5126G>A		intron_variant		1		ENSP00000389966
SLC24A5	ENST00000463289.1	n.62-5126G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4920 AN: 151876 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.00665

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000545

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0325 AC: 4938 AN: 151994 Hom.: 194 Cov.: 32 AF XY: 0.0335 AC XY: 2488 AN XY: 74310

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.0916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.00666

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.000545

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0118 Hom.: 31

Bravo AF: 0.0425

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.58

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: rs4775737; hg19: chr15-48421329;