chr2-161863591-T-G

Variant names:

• chr2-161863591-T-G
• rs1227929
• NM_001178015.2:c.766+529T>G

Variant summary

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

The NM_001178015.2(SLC4A10):​c.766+529T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,076 control chromosomes in the GnomAD database, including 27,098 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 0.60 (27098 hom., cov: 32)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 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.766+529T>G		intron	N/A	NP_001171486.1	Q6U841-1
	SLC4A10	NM_001354440.2		c.766+529T>G		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.802+529T>G		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.766+529T>G		intron	N/A	ENSP00000393066.1	Q6U841-1
	SLC4A10	ENST00000415876.6	TSL:1	c.766+529T>G		intron	N/A	ENSP00000395797.2	Q6U841-2
	SLC4A10	ENST00000461456.5	TSL:1	n.1003+529T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90466 AN: 151958 Hom.: 27089 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.595 AC: 90505 AN: 152076 Hom.: 27098 Cov.: 32 AF XY: 0.594 AC XY: 44176 AN XY: 74368

African (AFR) AF: 0.577 AC: 23934 AN: 41462

American (AMR) AF: 0.527 AC: 8049 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4383 AN: 5150

South Asian (SAS) AF: 0.553 AC: 2667 AN: 4826

European-Finnish (FIN) AF: 0.600 AC: 6349 AN: 10578

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41043 AN: 67988

Other (OTH) AF: 0.584 AC: 1233 AN: 2110

Alfa AF: 0.592 Hom.: 44508

Bravo AF: 0.589

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.72
PhyloP100		-0.29
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: rs1227929; hg19: chr2-162720101;