rs1051545

Variant names:

• chr3-27375508-T-C
• rs1051545
• NM_001321103.2:c.*1256A>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.*1256A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,114 control chromosomes in the GnomAD database, including 15,355 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 0.44 (15319 hom., cov: 32)
  • Exomes 𝑓: 0.40 (36 hom.)
• Consequence: SLC4A7 NM_001321103.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• Publications: 13 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

ENSG00000287348 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 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.*1256A>G		3_prime_UTR	Exon 26 of 26	NP_001308032.1	Q9Y6M7-7
	SLC4A7	NM_001321104.2		c.*1256A>G		3_prime_UTR	Exon 26 of 26	NP_001308033.1	Q9Y6M7-8
	SLC4A7	NM_003615.5		c.*1256A>G		3_prime_UTR	Exon 25 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.*1256A>G		3_prime_UTR	Exon 26 of 26	ENSP00000390394.1	Q9Y6M7-7
	SLC4A7	ENST00000295736.9	TSL:1	c.*1256A>G		3_prime_UTR	Exon 25 of 25	ENSP00000295736.5	Q9Y6M7-1
	SLC4A7	ENST00000428386.5	TSL:1	c.*1256A>G		3_prime_UTR	Exon 24 of 24	ENSP00000416368.1	Q9Y6M7-2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67099 AN: 151570 Hom.: 15318 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.404 AC: 173 AN: 428 Hom.: 36 Cov.: 0 AF XY: 0.364 AC XY: 94 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.403 AC: 170 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.442 AC: 67118 AN: 151686 Hom.: 15319 Cov.: 32 AF XY: 0.443 AC XY: 32817 AN XY: 74150

African (AFR) AF: 0.359 AC: 14891 AN: 41424

American (AMR) AF: 0.538 AC: 8219 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1951 AN: 3464

East Asian (EAS) AF: 0.191 AC: 992 AN: 5182

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4820

European-Finnish (FIN) AF: 0.447 AC: 4700 AN: 10518

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.481 AC: 32565 AN: 67704

Other (OTH) AF: 0.474 AC: 998 AN: 2106

Alfa AF: 0.480 Hom.: 3084

Bravo AF: 0.447

Asia WGS AF: 0.368 AC: 1270 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.80
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: rs1051545; hg19: chr3-27416999;