chr4-103031712-G-C

Variant summary

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

The NM_178833.7(SLC9B2):ā€‹c.1243C>Gā€‹(p.Pro415Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,611,908 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.010 ( 19 hom., cov: 32)
Exomes š‘“: 0.0022 ( 40 hom. )

Consequence

SLC9B2
NM_178833.7 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.42
Variant links:
Genes affected
SLC9B2 (HGNC:25143): (solute carrier family 9 member B2) Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]

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 (MetaRNN=0.0028415918).
BP6
Variant 4-103031712-G-C is Benign according to our data. Variant chr4-103031712-G-C is described in ClinVar as [Benign]. Clinvar id is 775219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1596/152178) while in subpopulation AFR AF= 0.0327 (1356/41522). AF 95% confidence interval is 0.0312. There are 19 homozygotes in gnomad4. There are 739 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC9B2NM_178833.7 linkuse as main transcriptc.1243C>G p.Pro415Ala missense_variant 10/12 ENST00000394785.9 NP_849155.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC9B2ENST00000394785.9 linkuse as main transcriptc.1243C>G p.Pro415Ala missense_variant 10/122 NM_178833.7 ENSP00000378265 P1Q86UD5-1

Frequencies

GnomAD3 genomes
AF:
0.0104
AC:
1589
AN:
152060
Hom.:
19
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0326
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00525
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00249
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00165
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00369
AC:
924
AN:
250410
Hom.:
11
AF XY:
0.00306
AC XY:
414
AN XY:
135354
show subpopulations
Gnomad AFR exome
AF:
0.0345
Gnomad AMR exome
AF:
0.00292
Gnomad ASJ exome
AF:
0.000996
Gnomad EAS exome
AF:
0.000598
Gnomad SAS exome
AF:
0.00207
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00141
Gnomad OTH exome
AF:
0.00329
GnomAD4 exome
AF:
0.00219
AC:
3202
AN:
1459730
Hom.:
40
Cov.:
30
AF XY:
0.00216
AC XY:
1565
AN XY:
726204
show subpopulations
Gnomad4 AFR exome
AF:
0.0324
Gnomad4 AMR exome
AF:
0.00317
Gnomad4 ASJ exome
AF:
0.00111
Gnomad4 EAS exome
AF:
0.000303
Gnomad4 SAS exome
AF:
0.00242
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00128
Gnomad4 OTH exome
AF:
0.00370
GnomAD4 genome
AF:
0.0105
AC:
1596
AN:
152178
Hom.:
19
Cov.:
32
AF XY:
0.00993
AC XY:
739
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0327
Gnomad4 AMR
AF:
0.00524
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.00270
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00165
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00297
Hom.:
2
Bravo
AF:
0.0122
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00130
AC:
5
ESP6500AA
AF:
0.0354
AC:
156
ESP6500EA
AF:
0.00128
AC:
11
ExAC
AF:
0.00414
AC:
503
Asia WGS
AF:
0.00549
AC:
20
AN:
3478
EpiCase
AF:
0.00240
EpiControl
AF:
0.00213

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
19
DANN
Benign
0.75
DEOGEN2
Benign
0.066
T;.;T;T;.
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.73
.;T;T;T;T
MetaRNN
Benign
0.0028
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;.;L;.;.
MutationTaster
Benign
0.95
D;D;D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.8
N;N;N;N;N
REVEL
Benign
0.047
Sift
Benign
0.44
T;T;T;T;T
Sift4G
Benign
0.76
T;T;T;T;T
Polyphen
0.014
B;.;B;B;B
Vest4
0.40
MVP
0.37
MPC
0.020
ClinPred
0.020
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.056
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs72943528; hg19: chr4-103952869; API