rs4775737

Variant names:

• chr15-48129132-G-A
• rs4775737
• NM_205850.3:c.302-5126G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A5	NM_205850.3	MANE Select	c.302-5126G>A		intron	N/A	NP_995322.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A5	ENST00000341459.8	TSL:1 MANE Select	c.302-5126G>A		intron	N/A	ENSP00000341550.3
	SLC24A5	ENST00000449382.2	TSL:1	c.122-5126G>A		intron	N/A	ENSP00000389966.2
	SLC24A5	ENST00000463289.1	TSL:3	n.62-5126G>A		intron	N/A

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

African (AFR) AF: 0.0720 AC: 2984 AN: 41456

American (AMR) AF: 0.0916 AC: 1399 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0769 AC: 398 AN: 5176

South Asian (SAS) AF: 0.00666 AC: 32 AN: 4806

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000545 AC: 37 AN: 67912

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0154 Hom.: 86

Bravo AF: 0.0425

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4775737; hg19: chr15-48421329;