rs147845115

Variant names:

• chr12-51484976-G-A
• rs147845115
• NM_001039960.3:c.2173-811G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001039960.3(SLC4A8):​c.2173-811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 152,250 control chromosomes in the GnomAD database, including 29 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 0.016 (29 hom., cov: 31)
• Consequence: SLC4A8 NM_001039960.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 9 publications found

Genes affected

SLC4A8 (HGNC:11034): (solute carrier family 4 member 8) The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

SLC4A8 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0157 (2392/152250) while in subpopulation NFE AF = 0.0224 (1521/68014). AF 95% confidence interval is 0.0214. There are 29 homozygotes in GnomAd4. There are 1139 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A8	NM_001039960.3	c.2173-811G>A		intron_variant	Intron 16 of 24	ENST00000453097.7	NP_001035049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A8	ENST00000453097.7	c.2173-811G>A		intron_variant	Intron 16 of 24	1	NM_001039960.3	ENSP00000405812.2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2396 AN: 152132 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0157 AC: 2392 AN: 152250 Hom.: 29 Cov.: 31 AF XY: 0.0153 AC XY: 1139 AN XY: 74452

African (AFR) AF: 0.00388 AC: 161 AN: 41544

American (AMR) AF: 0.0143 AC: 218 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4820

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0224 AC: 1521 AN: 68014

Other (OTH) AF: 0.0199 AC: 42 AN: 2110

Alfa AF: 0.0140 Hom.: 14

Bravo AF: 0.0139

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		0.083
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs147845115; hg19: chr12-51878760;