dbSNP rs9621415: SLC5A4:c.886-5G>A (chr22-32233039-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

2 publications found

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 was made for transcript

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

BP4

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

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.0106

AC:

2601

AN:

245692

AF XY:

0.0113

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 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

African (AFR)

AF:

0.00228

AC:

AN:

33344

American (AMR)

AF:

0.00412

AC:

182

AN:

44140

Ashkenazi Jewish (ASJ)

AF:

0.00496

AC:

129

AN:

26012

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39638

South Asian (SAS)

AF:

0.0104

AC:

894

AN:

85814

European-Finnish (FIN)

AF:

0.0120

AC:

639

AN:

53368

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0170

AC:

18859

AN:

1110496

Other (OTH)

AF:

0.0129

AC:

779

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

966

1931

2897

3862

4828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.0104

AC:

1584

AN:

152246

Hom.:

Cov.:

AF XY:

0.00987

AC XY:

735

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00260

AC:

108

AN:

41526

American (AMR)

AF:

0.00464

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0114

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0115

AC:

122

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0175

AC:

1192

AN:

68006

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0154

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

(source)

DANN

Benign

0.81

PhyloP100

2.0

Mutation Taster

=99/1

polymorphism

(source)

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

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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