Variant 15-65623968-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004727.3(SLC24A1):c.-113C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0082 in 923,956 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 42 hom. )

Consequence

SLC24A1
NM_004727.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.238

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 links:

LOC102723464 (HGNC:):

LOC102723464 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 15-65623968-C-T is Benign according to our data. Variant chr15-65623968-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 316783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00678 (1032/152152) while in subpopulation AMR AF= 0.0108 (165/15284). AF 95% confidence interval is 0.00963. There are 8 homozygotes in gnomad4. There are 458 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A1	NM_004727.3 link	c.-113C>T		5_prime_UTR_variant	2/10	ENST00000261892.11	NP_004718.1	O60721-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892 link	c.-113C>T		5_prime_UTR_variant	2/10	1	NM_004727.3	ENSP00000261892.6		O60721-1

Frequencies

GnomAD3 genomes

AF:

0.00679

AC:

1032

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00397

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0101

GnomAD4 exome

AF:

0.00848

AC:

6545

AN:

771804

Hom.:

Cov.:

AF XY:

0.00811

AC XY:

3205

AN XY:

395136

show subpopulations

Gnomad4 AFR exome

AF:

0.00190

Gnomad4 AMR exome

AF:

0.00752

Gnomad4 ASJ exome

AF:

0.000436

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000189

Gnomad4 FIN exome

AF:

0.00510

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00743

GnomAD4 genome

AF:

0.00678

AC:

1032

AN:

152152

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

458

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00397

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00841

Hom.:

Bravo

AF:

0.00696

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital stationary night blindness 1D

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.4

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over