rs868884

Variant names:

• chr12-51475314-G-A
• rs868884
• NM_001039960.3:c.2172+108G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-51475314-G-A
• chr12-51475314-G-T

Variant summary

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

The NM_001039960.3(SLC4A8):​c.2172+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,040,646 control chromosomes in the GnomAD database, including 148,299 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 0.54 (22262 hom., cov: 32)
  • Exomes 𝑓: 0.53 (126037 hom.)
• Consequence: SLC4A8 NM_001039960.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 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.2172+108G>A		intron	N/A	NP_001035049.1
	SLC4A8	NM_001405270.1		c.2136+108G>A		intron	N/A	NP_001392199.1
	SLC4A8	NM_001258401.3		c.2013+108G>A		intron	N/A	NP_001245330.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	ENST00000453097.7	TSL:1 MANE Select	c.2172+108G>A		intron	N/A	ENSP00000405812.2
	SLC4A8	ENST00000358657.7	TSL:1	c.2013+108G>A		intron	N/A	ENSP00000351483.4
	SLC4A8	ENST00000514353.7	TSL:1	c.2013+108G>A		intron	N/A	ENSP00000442561.2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81964 AN: 151916 Hom.: 22253 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.529 AC: 470303 AN: 888612 Hom.: 126037 AF XY: 0.529 AC XY: 241506 AN XY: 456930

African (AFR) AF: 0.579 AC: 12704 AN: 21952

American (AMR) AF: 0.419 AC: 15363 AN: 36638

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 10804 AN: 18488

East Asian (EAS) AF: 0.485 AC: 17856 AN: 36850

South Asian (SAS) AF: 0.517 AC: 32707 AN: 63276

European-Finnish (FIN) AF: 0.580 AC: 26980 AN: 46502

Middle Eastern (MID) AF: 0.465 AC: 2001 AN: 4306

European-Non Finnish (NFE) AF: 0.533 AC: 330329 AN: 619748

Other (OTH) AF: 0.528 AC: 21559 AN: 40852

GnomAD4 genome AF: 0.539 AC: 82022 AN: 152034 Hom.: 22262 Cov.: 32 AF XY: 0.539 AC XY: 40014 AN XY: 74298

African (AFR) AF: 0.576 AC: 23883 AN: 41464

American (AMR) AF: 0.471 AC: 7197 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2092 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2437 AN: 5174

South Asian (SAS) AF: 0.534 AC: 2575 AN: 4818

European-Finnish (FIN) AF: 0.579 AC: 6109 AN: 10556

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35901 AN: 67970

Other (OTH) AF: 0.524 AC: 1106 AN: 2112

Alfa AF: 0.537 Hom.: 4050

Bravo AF: 0.530

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.31
PhyloP100		-0.81
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

Other links and lift over

dbSNP: rs868884; hg19: chr12-51869098; COSMIC: COSV60656867; COSMIC: COSV60656867;