Genetic Variant NM_004727.3:c.2884-432C>T (chr15-65652210-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004727.3(SLC24A1):c.2884-432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 302,050 control chromosomes in the GnomAD database, including 45,533 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 0.57 ( 27042 hom., cov: 31)

Exomes 𝑓: 0.48 ( 18491 hom. )

Consequence

SLC24A1
NM_004727.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.13

Publications

5 publications found

Variant links:

Genes affected

SLC24A1 (HGNC:10975): (solute carrier family 24 member 1) This gene encodes a member of the potassium-dependent sodium/calcium exchanger protein family. The encoded protein plays an important role in sodium/calcium exchange in retinal rod and cone photoreceptors by mediating the extrusion of one calcium ion and one potassium ion in exchange for four sodium ions. Mutations in this gene may play a role in congenital stationary night blindness. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SLC24A1 Gene-Disease associations (from GenCC):

congenital stationary night blindness 1D
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC24A1 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A1	NM_004727.3 link	c.2884-432C>T		intron_variant	Intron 8 of 9	ENST00000261892.11	NP_004718.1	O60721-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11 link	c.2884-432C>T		intron_variant	Intron 8 of 9	1	NM_004727.3	ENSP00000261892.6		O60721-1

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85970

AN:

151926

Hom.:

26999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.845

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.546

GnomAD4 exome

AF:

0.478

AC:

71753

AN:

150006

Hom.:

18491

Cov.:

AF XY:

0.487

AC XY:

39102

AN XY:

80288

show subpopulations

African (AFR)

AF:

0.852

AC:

3807

AN:

4468

American (AMR)

AF:

0.472

AC:

2536

AN:

5370

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1518

AN:

3858

East Asian (EAS)

AF:

0.805

AC:

5024

AN:

6244

South Asian (SAS)

AF:

0.548

AC:

13802

AN:

25176

European-Finnish (FIN)

AF:

0.447

AC:

3189

AN:

7130

Middle Eastern (MID)

AF:

0.489

AC:

278

AN:

568

European-Non Finnish (NFE)

AF:

0.425

AC:

38081

AN:

89664

Other (OTH)

AF:

0.467

AC:

3518

AN:

7528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1639

3279

4918

6558

8197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.566

AC:

86078

AN:

152044

Hom.:

27042

Cov.:

AF XY:

0.565

AC XY:

41960

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.845

AC:

35052

AN:

41480

American (AMR)

AF:

0.453

AC:

6912

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1406

AN:

3470

East Asian (EAS)

AF:

0.808

AC:

4179

AN:

5174

South Asian (SAS)

AF:

0.566

AC:

2729

AN:

4822

European-Finnish (FIN)

AF:

0.463

AC:

4885

AN:

10544

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29336

AN:

67966

Other (OTH)

AF:

0.549

AC:

1158

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1654

3307

4961

6614

8268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.483

Hom.:

10358

Bravo

AF:

0.579

Asia WGS

AF:

0.673

AC:

2341

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.045

(source)

DANN

Benign

0.41

PhyloP100

-3.1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over