12-51512565-C-A

Variant names:

• chr12-51512565-C-A
• rs1493193
• NM_001039960.3:c.*5127C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039960.3(SLC4A8):​c.*5127C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,402 control chromosomes in the GnomAD database, including 65,411 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 0.93 (65335 hom., cov: 31)
  • Exomes 𝑓: 0.95 (76 hom.)
• Consequence: SLC4A8 NM_001039960.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039960.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	NM_001039960.3	MANE Select	c.*5127C>A		3_prime_UTR	Exon 25 of 25	NP_001035049.1
	SLC4A8	NM_001405270.1		c.*5127C>A		3_prime_UTR	Exon 25 of 25	NP_001392199.1
	SLC4A8	NM_001258401.3		c.*5127C>A		3_prime_UTR	Exon 25 of 25	NP_001245330.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	ENST00000453097.7	TSL:1 MANE Select	c.*5127C>A		3_prime_UTR	Exon 25 of 25	ENSP00000405812.2
	SLC4A8	ENST00000358657.7	TSL:1	c.*5127C>A		3_prime_UTR	Exon 25 of 25	ENSP00000351483.4

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140862 AN: 152118 Hom.: 65285 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.926

GnomAD4 exome AF: 0.952 AC: 158 AN: 166 Hom.: 76 Cov.: 0 AF XY: 0.935 AC XY: 101 AN XY: 108

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 14 AN: 14

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.944 AC: 119 AN: 126

Other (OTH) AF: 0.938 AC: 15 AN: 16

GnomAD4 genome AF: 0.926 AC: 140969 AN: 152236 Hom.: 65335 Cov.: 31 AF XY: 0.925 AC XY: 68833 AN XY: 74434

African (AFR) AF: 0.898 AC: 37267 AN: 41518

American (AMR) AF: 0.898 AC: 13735 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3386 AN: 3472

East Asian (EAS) AF: 0.919 AC: 4765 AN: 5184

South Asian (SAS) AF: 0.899 AC: 4325 AN: 4812

European-Finnish (FIN) AF: 0.950 AC: 10075 AN: 10608

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64293 AN: 68028

Other (OTH) AF: 0.926 AC: 1959 AN: 2116

Alfa AF: 0.933 Hom.: 11721

Bravo AF: 0.921

Asia WGS AF: 0.899 AC: 3128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		0.12

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: rs1493193; hg19: chr12-51906349;