chr2-161839904-C-T

Variant names:

• chr2-161839904-C-T
• rs2084543
• NM_001178015.2:c.393C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001354455.2(SLC4A10):​c.-293C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,613,532 control chromosomes in the GnomAD database, including 4,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (368 hom., cov: 32)
  • Exomes 𝑓: 0.072 (4235 hom.)
• Consequence: SLC4A10 NM_001354455.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.322
• Publications: 13 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 2-161839904-C-T is Benign according to our data. Variant chr2-161839904-C-T is described in ClinVar as Benign. ClinVar VariationId is 586611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354455.2. 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.393C>T	p.Asp131Asp	synonymous	Exon 4 of 27	NP_001171486.1	Q6U841-1
	SLC4A10	NM_001354455.2		c.-293C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 27	NP_001341384.1
	SLC4A10	NM_001354440.2		c.393C>T	p.Asp131Asp	synonymous	Exon 4 of 26	NP_001341369.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.393C>T	p.Asp131Asp	synonymous	Exon 4 of 27	ENSP00000393066.1	Q6U841-1
	SLC4A10	ENST00000415876.6	TSL:1	c.393C>T	p.Asp131Asp	synonymous	Exon 4 of 26	ENSP00000395797.2	Q6U841-2
	SLC4A10	ENST00000461456.5	TSL:1	n.630C>T		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9230 AN: 151984 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0861

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.0699

GnomAD2 exomes AF: 0.0736 AC: 18345 AN: 249270 AF XY: 0.0758

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.0471

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0755

Gnomad OTH exome AF: 0.0762

GnomAD4 exome AF: 0.0724 AC: 105851 AN: 1461430 Hom.: 4235 Cov.: 31 AF XY: 0.0735 AC XY: 53468 AN XY: 727010

African (AFR) AF: 0.0109 AC: 365 AN: 33474

American (AMR) AF: 0.0482 AC: 2157 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 889 AN: 26132

East Asian (EAS) AF: 0.121 AC: 4789 AN: 39698

South Asian (SAS) AF: 0.0790 AC: 6809 AN: 86238

European-Finnish (FIN) AF: 0.112 AC: 5954 AN: 53384

Middle Eastern (MID) AF: 0.0406 AC: 234 AN: 5768

European-Non Finnish (NFE) AF: 0.0725 AC: 80633 AN: 1111670

Other (OTH) AF: 0.0666 AC: 4021 AN: 60358

GnomAD4 genome AF: 0.0607 AC: 9234 AN: 152102 Hom.: 368 Cov.: 32 AF XY: 0.0637 AC XY: 4735 AN XY: 74344

African (AFR) AF: 0.0135 AC: 562 AN: 41512

American (AMR) AF: 0.0652 AC: 996 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.133 AC: 689 AN: 5164

South Asian (SAS) AF: 0.0868 AC: 417 AN: 4806

European-Finnish (FIN) AF: 0.117 AC: 1232 AN: 10558

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0729 AC: 4955 AN: 68004

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0651 Hom.: 824

Bravo AF: 0.0550

Asia WGS AF: 0.101 AC: 352 AN: 3478

EpiCase AF: 0.0747

EpiControl AF: 0.0786

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2084543; hg19: chr2-162696414; COSMIC: COSV55792824; COSMIC: COSV55792824;