2-219629139-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_005070.4(SLC4A3):c.218-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,572,930 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (30 hom.)
• Consequence: SLC4A3 NM_005070.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002269
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86

Genes affected

SLC4A3 (HGNC:11029): (solute carrier family 4 member 3) The protein encoded by this gene is a plasma membrane anion exchange protein. The encoded protein has been found in brain, heart, kidney, small intestine, and lung. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 2-219629139-C-T is Benign according to our data. Variant chr2-219629139-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A3	NM_005070.4	c.218-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000358055.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A3	ENST00000358055.8	c.218-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005070.4	P1

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 513 AN: 152106 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00543

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00301 AC: 655 AN: 217814 Hom.: 4 AF XY: 0.00297 AC XY: 349 AN XY: 117564

Gnomad AFR exome AF: 0.000925

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.000964

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00198

Gnomad FIN exome AF: 0.00218

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00483 AC: 6856 AN: 1420706 Hom.: 30 Cov.: 33 AF XY: 0.00467 AC XY: 3277 AN XY: 702236

Gnomad4 AFR exome AF: 0.000681

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00127

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00189

Gnomad4 FIN exome AF: 0.00213

Gnomad4 NFE exome AF: 0.00566

Gnomad4 OTH exome AF: 0.00442

GnomAD4 genome AF: 0.00337 AC: 513 AN: 152224 Hom.: 2 Cov.: 32 AF XY: 0.00349 AC XY: 260 AN XY: 74412

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00543

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00449 Hom.: 2

Bravo AF: 0.00331

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SLC4A3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	12
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.070		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: rs41272705; hg19: chr2-220493861;