3-27391504-T-C

Variant names:

• chr3-27391504-T-C
• rs2307032
• NM_001321103.2:c.3186+236A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321103.2(SLC4A7):​c.3186+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,104 control chromosomes in the GnomAD database, including 6,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6745 hom., cov: 32)
• Consequence: SLC4A7 NM_001321103.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

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.3186+236A>G		intron	N/A	NP_001308032.1	Q9Y6M7-7
	SLC4A7	NM_001321104.2		c.3147+236A>G		intron	N/A	NP_001308033.1	Q9Y6M7-8
	SLC4A7	NM_003615.5		c.3159+236A>G		intron	N/A	NP_003606.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A7	ENST00000454389.6	TSL:1 MANE Select	c.3186+236A>G		intron	N/A	ENSP00000390394.1	Q9Y6M7-7
	SLC4A7	ENST00000440156.5	TSL:1	c.3147+236A>G		intron	N/A	ENSP00000414797.1	Q9Y6M7-8
	SLC4A7	ENST00000295736.9	TSL:1	c.3159+236A>G		intron	N/A	ENSP00000295736.5	Q9Y6M7-1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40364 AN: 151986 Hom.: 6743 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40372 AN: 152104 Hom.: 6745 Cov.: 32 AF XY: 0.268 AC XY: 19905 AN XY: 74344

African (AFR) AF: 0.0632 AC: 2625 AN: 41556

American (AMR) AF: 0.307 AC: 4684 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2938 AN: 5156

South Asian (SAS) AF: 0.201 AC: 971 AN: 4820

European-Finnish (FIN) AF: 0.365 AC: 3847 AN: 10542

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23290 AN: 67962

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.312 Hom.: 24883

Bravo AF: 0.255

Asia WGS AF: 0.336 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.69
PhyloP100		-2.9
Mutation Taster		=100/0	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: rs2307032; hg19: chr3-27432995;