3-27395104-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001321103.2(SLC4A7):c.2715A>G(p.Pro905=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000785 in 1,580,514 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00066 (4 hom.)
• Consequence: SLC4A7 NM_001321103.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

Genes affected

SLC4A7 (HGNC:11033): (solute carrier family 4 member 7) This locus encodes a sodium bicarbonate cotransporter. The encoded transmembrane protein appears to transport sodium and bicarbonate ions in a 1:1 ratio, and is thus considered an electroneutral cotransporter. The encoded protein likely plays a critical role in regulation of intracellular pH involved in visual and auditory sensory transmission. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-27395104-T-C is Benign according to our data. Variant chr3-27395104-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A7	NM_001321103.2	c.2715A>G	p.Pro905=	synonymous_variant	19/26	ENST00000454389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A7	ENST00000454389.6	c.2715A>G	p.Pro905=	synonymous_variant	19/26	1	NM_001321103.2

Frequencies

GnomAD3 genomes AF: 0.00196 AC: 299 AN: 152238 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.000994 AC: 215 AN: 216402 Hom.: 0 AF XY: 0.000893 AC XY: 105 AN XY: 117524

Gnomad AFR exome AF: 0.00334

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00413

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000830

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000543

Gnomad OTH exome AF: 0.00275

GnomAD4 exome AF: 0.000659 AC: 941 AN: 1428158 Hom.: 4 Cov.: 30 AF XY: 0.000652 AC XY: 463 AN XY: 710176

Gnomad4 AFR exome AF: 0.00274

Gnomad4 AMR exome AF: 0.00301

Gnomad4 ASJ exome AF: 0.00556

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000376

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000444

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.00196 AC: 299 AN: 152356 Hom.: 1 Cov.: 33 AF XY: 0.00205 AC XY: 153 AN XY: 74510

Gnomad4 AFR AF: 0.00351

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.00252

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC4A7-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 24, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	7.0
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs148520298; hg19: chr3-27436595;