chr2-219629139-C-T

Variant names:

• chr2-219629139-C-T
• rs41272705
• NM_005070.4:c.218-5C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_005070.4(SLC4A3):​c.218-5C>T variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.0002269
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.86
• Publications: 1 publications found

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]

SLC4A3 Gene-Disease associations (from GenCC):

• short QT syndrome 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• short QT syndrome

  Inheritance: AD Classification: MODERATE Submitted by: G2P, ClinGen
• autosomal dominant distal renal tubular acidosis

  Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -14 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 Benign/Likely_benign. ClinVar VariationId is 2651937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 513 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005070.4. 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
	SLC4A3	NM_005070.4	MANE Select	c.218-5C>T		splice_region intron	N/A	NP_005061.3	P48751-1
	SLC4A3	NM_001326559.2		c.218-5C>T		splice_region intron	N/A	NP_001313488.2	P48751-3
	SLC4A3	NM_201574.3		c.218-5C>T		splice_region intron	N/A	NP_963868.3	P48751-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A3	ENST00000358055.8	TSL:1 MANE Select	c.218-5C>T		splice_region intron	N/A	ENSP00000350756.3	P48751-1
	SLC4A3	ENST00000273063.10	TSL:1	c.218-5C>T		splice_region intron	N/A	ENSP00000273063.6	P48751-3
	SLC4A3	ENST00000425141.5	TSL:1	n.218-5C>T		splice_region intron	N/A	ENSP00000396863.1	F8WD49

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

GnomAD2 exomes AF: 0.00301 AC: 655 AN: 217814 AF XY: 0.00297

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 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

African (AFR) AF: 0.000681 AC: 22 AN: 32318

American (AMR) AF: 0.00262 AC: 105 AN: 40012

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 30 AN: 23584

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39266

South Asian (SAS) AF: 0.00189 AC: 153 AN: 80776

European-Finnish (FIN) AF: 0.00213 AC: 108 AN: 50752

Middle Eastern (MID) AF: 0.00181 AC: 10 AN: 5512

European-Non Finnish (NFE) AF: 0.00566 AC: 6168 AN: 1089930

Other (OTH) AF: 0.00442 AC: 259 AN: 58556

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

African (AFR) AF: 0.000722 AC: 30 AN: 41532

American (AMR) AF: 0.00438 AC: 67 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4820

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00543 AC: 369 AN: 68000

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00459 Hom.: 2

Bravo AF: 0.00331

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		1.9
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs41272705; hg19: chr2-220493861;