dbSNP rs9621415: SLC5A4:c.886-5G>A (chr22-32233039-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014227.3(SLC5A4):c.886-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,611,064 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 32)

Exomes 𝑓: 0.015 ( 177 hom. )

Consequence

SLC5A4
NM_014227.3 splice_region, intron

Scores

Splicing: ADA: 0.2765

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.97

Variant links:

Genes affected

SLC5A4 (HGNC:11039): (solute carrier family 5 member 4) Predicted to enable glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in sodium ion transport. Predicted to act upstream of or within proton transmembrane transport. Predicted to be active in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A4 links:

SLC5A4-AS1 (HGNC:53163): (SLC5A4 antisense RNA 1)

SLC5A4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 22-32233039-C-T is Benign according to our data. Variant chr22-32233039-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0104 (1584/152246) while in subpopulation NFE AF= 0.0175 (1192/68006). AF 95% confidence interval is 0.0167. There are 14 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A4	NM_014227.3 link	c.886-5G>A		splice_region_variant, intron_variant	Intron 8 of 14	ENST00000266086.6	NP_055042.1	Q9NY91

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC5A4	ENST00000266086.6 link	c.886-5G>A	splice_region_variant, intron_variant	Intron 8 of 14	1	NM_014227.3	ENSP00000266086.3	Q9NY91
SLC5A4-AS1	ENST00000434942.2 link	n.507+3667C>T	intron_variant	Intron 3 of 4	3
SLC5A4-AS1	ENST00000452181.2 link	n.274+25763C>T	intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1584

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0106

AC:

2601

AN:

245692

Hom.:

AF XY:

0.0113

AC XY:

1499

AN XY:

132950

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0123

GnomAD4 exome

AF:

0.0148

AC:

21574

AN:

1458818

Hom.:

177

Cov.:

AF XY:

0.0147

AC XY:

10671

AN XY:

725502

show subpopulations

Gnomad4 AFR exome

AF:

0.00228

Gnomad4 AMR exome

AF:

0.00412

Gnomad4 ASJ exome

AF:

0.00496

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0104

AC:

1584

AN:

152246

Hom.:

Cov.:

AF XY:

0.00987

AC XY:

735

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0114

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.00921

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0135

EpiControl

AF:

0.0125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.28

dbscSNV1_RF

Benign

0.55

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.97

Position offset: -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

Computational scores

Splicing

Publications

LitVar

Other links and lift over