NM_205850.3:c.301+4412A>G

Variant names:

• chr15-48126448-A-G
• rs2675347
• NM_205850.3:c.301+4412A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.93).
• 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 rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.301+4412A>G		intron_variant	Intron 2 of 8	ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.301+4412A>G		intron_variant	Intron 2 of 7		XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.301+4412A>G		intron_variant	Intron 2 of 8	1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.121+5283A>G		intron_variant	Intron 1 of 7	1		ENSP00000389966.2
SLC24A5	ENST00000463289.1	n.61+4412A>G		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.568 AC: 23570 AN: 41462

American (AMR) AF: 0.169 AC: 2591 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2468 AN: 5170

South Asian (SAS) AF: 0.163 AC: 787 AN: 4818

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00788 AC: 536 AN: 68024

Other (OTH) AF: 0.170 AC: 360 AN: 2114

Alfa AF: 0.0641 Hom.: 875

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
PhyloP100		-0.21
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: rs2675347; hg19: chr15-48418645;