chr22-32225632-C-T

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

2

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

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=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC5A4NM_014227.3 linkc.1449+23G>A intron_variant Intron 12 of 14 ENST00000266086.6 NP_055042.1 Q9NY91

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC5A4ENST00000266086.6 linkc.1449+23G>A intron_variant Intron 12 of 14 1 NM_014227.3 ENSP00000266086.3 Q9NY91
SLC5A4-AS1ENST00000434942.2 linkn.225-3458C>T intron_variant Intron 2 of 4 3
SLC5A4-AS1ENST00000452181.2 linkn.274+18356C>T intron_variant Intron 2 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.507
AC:
76908
AN:
151834
Hom.:
21027
Cov.:
32
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.:
22
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
0
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
0
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.:
32
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
0
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
0
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 v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.066
DANN
Benign
0.46
PhyloP100
-2.2
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2294208; hg19: chr22-32621619; COSMIC: COSV56669260; API