2-161965134-C-T

Variant names:

• chr2-161965134-C-T
• rs61748243
• NM_001178015.2:c.3120C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001178015.2(SLC4A10):​c.3120C>T​(p.Pro1040Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,609,384 control chromosomes in the GnomAD database, including 363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (41 hom., cov: 32)
  • Exomes 𝑓: 0.015 (322 hom.)
• Consequence: SLC4A10 NM_001178015.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.611
• Publications: 5 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

ENSG00000296511 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 2-161965134-C-T is Benign according to our data. Variant chr2-161965134-C-T is described in ClinVar as Benign. ClinVar VariationId is 586610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.611 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A10	NM_001178015.2	c.3120C>T	p.Pro1040Pro	synonymous_variant	Exon 23 of 27	ENST00000446997.6	NP_001171486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6	c.3120C>T	p.Pro1040Pro	synonymous_variant	Exon 23 of 27	1	NM_001178015.2	ENSP00000393066.1

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2011 AN: 151086 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00363

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.00337

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.0192 AC: 4761 AN: 247378 AF XY: 0.0193

Gnomad AFR exome AF: 0.00423

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.00848

Gnomad EAS exome AF: 0.0948

Gnomad FIN exome AF: 0.00419

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0151 AC: 22042 AN: 1458182 Hom.: 322 Cov.: 31 AF XY: 0.0155 AC XY: 11220 AN XY: 725354

African (AFR) AF: 0.00362 AC: 121 AN: 33396

American (AMR) AF: 0.0166 AC: 741 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00746 AC: 194 AN: 26012

East Asian (EAS) AF: 0.0828 AC: 3269 AN: 39504

South Asian (SAS) AF: 0.0261 AC: 2241 AN: 85778

European-Finnish (FIN) AF: 0.00451 AC: 240 AN: 53254

Middle Eastern (MID) AF: 0.0167 AC: 96 AN: 5752

European-Non Finnish (NFE) AF: 0.0127 AC: 14070 AN: 1109772

Other (OTH) AF: 0.0178 AC: 1070 AN: 60170

GnomAD4 genome AF: 0.0133 AC: 2014 AN: 151202 Hom.: 41 Cov.: 32 AF XY: 0.0140 AC XY: 1035 AN XY: 73838

African (AFR) AF: 0.00362 AC: 149 AN: 41182

American (AMR) AF: 0.0151 AC: 229 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 33 AN: 3468

East Asian (EAS) AF: 0.0995 AC: 515 AN: 5176

South Asian (SAS) AF: 0.0310 AC: 147 AN: 4746

European-Finnish (FIN) AF: 0.00337 AC: 35 AN: 10392

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 876 AN: 67796

Other (OTH) AF: 0.0119 AC: 25 AN: 2102

Alfa AF: 0.0103 Hom.: 2

Bravo AF: 0.0132

Asia WGS AF: 0.0650 AC: 224 AN: 3478

EpiCase AF: 0.0121

EpiControl AF: 0.0118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		-0.61
Mutation Taster		=92/8	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: rs61748243; hg19: chr2-162821644; COSMIC: COSV55794496;