NM_001178015.2:c.2104-768T>C

Variant names:

• chr2-161946798-T-C
• rs1913807
• NM_001178015.2:c.2104-768T>C

Variant summary

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

The NM_001178015.2(SLC4A10):​c.2104-768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 151,976 control chromosomes in the GnomAD database, including 51,384 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 0.82 (51384 hom., cov: 31)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 4 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):

• neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A10	NM_001178015.2	c.2104-768T>C		intron_variant	Intron 16 of 26	ENST00000446997.6	NP_001171486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6	c.2104-768T>C		intron_variant	Intron 16 of 26	1	NM_001178015.2	ENSP00000393066.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124472 AN: 151858 Hom.: 51312 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.820 AC: 124605 AN: 151976 Hom.: 51384 Cov.: 31 AF XY: 0.824 AC XY: 61187 AN XY: 74286

African (AFR) AF: 0.892 AC: 37015 AN: 41488

American (AMR) AF: 0.834 AC: 12685 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2731 AN: 3468

East Asian (EAS) AF: 0.966 AC: 4983 AN: 5158

South Asian (SAS) AF: 0.890 AC: 4285 AN: 4816

European-Finnish (FIN) AF: 0.789 AC: 8350 AN: 10582

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51958 AN: 67934

Other (OTH) AF: 0.799 AC: 1688 AN: 2112

Alfa AF: 0.742 Hom.: 3345

Bravo AF: 0.826

Asia WGS AF: 0.913 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.59
PhyloP100		-0.71
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: rs1913807; hg19: chr2-162803308;