chr2-161695208-G-A

Variant names:

• chr2-161695208-G-A
• rs1399650
• NM_001178015.2:c.48+70642G>A

Variant summary

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

The NM_001178015.2(SLC4A10):​c.48+70642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,864 control chromosomes in the GnomAD database, including 48,906 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 0.80 (48906 hom., cov: 31)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 2 publications found

Genes affected

SLC4A10 (HGNC:13811): (solute carrier family 4 member 10) This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

SLC4A10 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, PanelApp Australia, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178015.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	NM_001178015.2	MANE Select	c.48+70642G>A		intron	N/A	NP_001171486.1	Q6U841-1
	SLC4A10	NM_001354440.2		c.48+70642G>A		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.-50-15410G>A		intron	N/A	NP_001341389.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.48+70642G>A		intron	N/A	ENSP00000393066.1	Q6U841-1
	SLC4A10	ENST00000415876.6	TSL:1	c.48+70642G>A		intron	N/A	ENSP00000395797.2	Q6U841-2
	SLC4A10	ENST00000461456.5	TSL:1	n.150-13486G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121514 AN: 151746 Hom.: 48880 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.801 AC: 121585 AN: 151864 Hom.: 48906 Cov.: 31 AF XY: 0.799 AC XY: 59289 AN XY: 74218

African (AFR) AF: 0.714 AC: 29569 AN: 41434

American (AMR) AF: 0.843 AC: 12848 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2982 AN: 3472

East Asian (EAS) AF: 0.855 AC: 4430 AN: 5180

South Asian (SAS) AF: 0.823 AC: 3953 AN: 4804

European-Finnish (FIN) AF: 0.774 AC: 8153 AN: 10536

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56910 AN: 67882

Other (OTH) AF: 0.806 AC: 1702 AN: 2112

Alfa AF: 0.831 Hom.: 211380

Bravo AF: 0.803

Asia WGS AF: 0.828 AC: 2860 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.045
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: rs1399650; hg19: chr2-162551718;