dbSNP rs2294208: SLC5A4:c.1449+23G>A (chr22-32225632-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_014227.3(SLC5A4):c.1449+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,534,040 control chromosomes in the GnomAD database, including 166,117 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 0.51 ( 21069 hom., cov: 32)

Exomes 𝑓: 0.45 ( 145048 hom. )

Consequence

SLC5A4
NM_014227.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

12 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

new If you want to explore the variant's impact on the transcript NM_014227.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014227.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A4	NM_014227.3	MANE Select	c.1449+23G>A		intron	N/A	NP_055042.1	Q9NY91
	SLC5A4-AS1	NR_149072.1		n.274+18356C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC5A4	ENST00000266086.6	TSL:1 MANE Select	c.1449+23G>A	intron	N/A	ENSP00000266086.3	Q9NY91
SLC5A4-AS1	ENST00000434942.2	TSL:3	n.225-3458C>T	intron	N/A
SLC5A4-AS1	ENST00000452181.2	TSL:5	n.274+18356C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76908

AN:

151834

Hom.:

21027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.461

GnomAD2 exomes

AF:

0.424

AC:

89678

AN:

211306

AF XY:

0.426

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.451

AC:

623226

AN:

1382088

Hom.:

145048

Cov.:

AF XY:

0.449

AC XY:

308359

AN XY:

686826

show subpopulations

African (AFR)

AF:

0.720

AC:

21533

AN:

29924

American (AMR)

AF:

0.319

AC:

10967

AN:

34420

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

10208

AN:

23916

East Asian (EAS)

AF:

0.124

AC:

4725

AN:

38144

South Asian (SAS)

AF:

0.402

AC:

30613

AN:

76188

European-Finnish (FIN)

AF:

0.413

AC:

21654

AN:

52372

Middle Eastern (MID)

AF:

0.458

AC:

2523

AN:

5508

European-Non Finnish (NFE)

AF:

0.465

AC:

495045

AN:

1064418

Other (OTH)

AF:

0.454

AC:

25958

AN:

57198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

14085

28170

42255

56340

70425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14792

29584

44376

59168

73960

<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:

0.507

AC:

77013

AN:

151952

Hom.:

21069

Cov.:

AF XY:

0.499

AC XY:

37039

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.710

AC:

29447

AN:

41450

American (AMR)

AF:

0.390

AC:

5955

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1550

AN:

3468

East Asian (EAS)

AF:

0.143

AC:

743

AN:

5180

South Asian (SAS)

AF:

0.393

AC:

1893

AN:

4818

European-Finnish (FIN)

AF:

0.408

AC:

4302

AN:

10542

Middle Eastern (MID)

AF:

0.455

AC:

133

AN:

292

European-Non Finnish (NFE)

AF:

0.465

AC:

31544

AN:

67898

Other (OTH)

AF:

0.460

AC:

971

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1800

3600

5400

7200

9000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.486

Hom.:

4456

Bravo

AF:

0.512

Asia WGS

AF:

0.344

AC:

1200

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.066

(source)

DANN

Benign

0.46

PhyloP100

-2.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over