dbSNP rs2459391: SLC24A5:c.301+835A>G (chr15-48122871-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_205850.3(SLC24A5):c.301+835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 152,168 control chromosomes in the GnomAD database, including 1,323 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 0.080 ( 1323 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC24A5
NM_205850.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

Publications

6 publications found

Variant links:

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)

SLC24A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3 link	c.301+835A>G		intron_variant	Intron 2 of 8	ENST00000341459.8	NP_995322.1	Q71RS6-1
SLC24A5	XM_047432394.1 link	c.301+835A>G		intron_variant	Intron 2 of 7		XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC24A5	ENST00000341459.8 link	c.301+835A>G	intron_variant	Intron 2 of 8	1	NM_205850.3	ENSP00000341550.3	Q71RS6-1
SLC24A5	ENST00000449382.2 link	c.121+1706A>G	intron_variant	Intron 1 of 7	1		ENSP00000389966.2	Q71RS6-2
SLC24A5	ENST00000482911.2 link	c.*767A>G	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000453395.1	H0YLZ0
SLC24A5	ENST00000463289.1 link	n.61+835A>G	intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0797

AC:

12124

AN:

152050

Hom.:

1308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0762

Gnomad SAS

AF:

0.0437

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0589

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0801

AC:

12188

AN:

152168

Hom.:

1323

Cov.:

AF XY:

0.0804

AC XY:

5985

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.236

AC:

9784

AN:

41450

American (AMR)

AF:

0.105

AC:

1601

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0765

AC:

397

AN:

5188

South Asian (SAS)

AF:

0.0435

AC:

210

AN:

4826

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000764

AC:

AN:

68028

Other (OTH)

AF:

0.0588

AC:

124

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

475

949

1424

1898

2373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0646

Hom.:

167

Bravo

AF:

0.0959

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.17

(source)

DANN

Benign

0.30

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over