NM_001321103.2:c.2496T>C

Variant names:

• chr3-27398285-A-G
• rs372420522
• NM_001321103.2:c.2496T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_001321103.2(SLC4A7):​c.2496T>C​(p.Asp832Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SLC4A7 NM_001321103.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.18
• Publications: 1 publications found

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]

SLC4A7 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• cone-rod dystrophy

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-27398285-A-G is Benign according to our data. Variant chr3-27398285-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3053863.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.18 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321103.2. 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
	SLC4A7	NM_001321103.2	MANE Select	c.2496T>C	p.Asp832Asp	synonymous	Exon 17 of 26	NP_001308032.1	Q9Y6M7-7
	SLC4A7	NM_001321104.2		c.2457T>C	p.Asp819Asp	synonymous	Exon 17 of 26	NP_001308033.1	Q9Y6M7-8
	SLC4A7	NM_003615.5		c.2469T>C	p.Asp823Asp	synonymous	Exon 17 of 25	NP_003606.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A7	ENST00000454389.6	TSL:1 MANE Select	c.2496T>C	p.Asp832Asp	synonymous	Exon 17 of 26	ENSP00000390394.1	Q9Y6M7-7
	SLC4A7	ENST00000440156.5	TSL:1	c.2457T>C	p.Asp819Asp	synonymous	Exon 17 of 26	ENSP00000414797.1	Q9Y6M7-8
	SLC4A7	ENST00000295736.9	TSL:1	c.2469T>C	p.Asp823Asp	synonymous	Exon 17 of 25	ENSP00000295736.5	Q9Y6M7-1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251210 AF XY: 0.00000737

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461222 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726942

African (AFR) AF: 0.000179 AC: 6 AN: 33460

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111526

Other (OTH) AF: 0.0000331 AC: 2 AN: 60358

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74346

African (AFR) AF: 0.000169 AC: 7 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000147

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC4A7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.1
DANN	Benign	0.55
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs372420522; hg19: chr3-27439776;