NM_001321103.2:c.*2242G>A

Variant names:

• chr3-27374522-C-T
• rs4973768
• NM_001321103.2:c.*2242G>A

Variant summary

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

The NM_001321103.2(SLC4A7):​c.*2242G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,260 control chromosomes in the GnomAD database, including 15,155 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 (15123 hom., cov: 33)
  • Exomes 𝑓: 0.40 (32 hom.)
• Consequence: SLC4A7 NM_001321103.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 199 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):

• 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A7	NM_001321103.2	MANE Select	c.*2242G>A		3_prime_UTR	Exon 26 of 26	NP_001308032.1
	SLC4A7	NM_001321104.2		c.*2242G>A		3_prime_UTR	Exon 26 of 26	NP_001308033.1
	SLC4A7	NM_003615.5		c.*2242G>A		3_prime_UTR	Exon 25 of 25	NP_003606.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A7	ENST00000454389.6	TSL:1 MANE Select	c.*2242G>A		3_prime_UTR	Exon 26 of 26	ENSP00000390394.1
	SLC4A7	ENST00000295736.9	TSL:1	c.*2242G>A		3_prime_UTR	Exon 25 of 25	ENSP00000295736.5
	SLC4A7	ENST00000428386.5	TSL:1	c.*2242G>A		3_prime_UTR	Exon 24 of 24	ENSP00000416368.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66738 AN: 151730 Hom.: 15122 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.402 AC: 165 AN: 410 Hom.: 32 Cov.: 0 AF XY: 0.360 AC XY: 90 AN XY: 250

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: 0.401 AC: 162 AN: 404

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: 0.440 AC: 66758 AN: 151850 Hom.: 15123 Cov.: 33 AF XY: 0.440 AC XY: 32658 AN XY: 74202

African (AFR) AF: 0.358 AC: 14835 AN: 41474

American (AMR) AF: 0.537 AC: 8193 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1951 AN: 3468

East Asian (EAS) AF: 0.192 AC: 993 AN: 5172

South Asian (SAS) AF: 0.441 AC: 2130 AN: 4830

European-Finnish (FIN) AF: 0.447 AC: 4713 AN: 10542

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32304 AN: 67788

Other (OTH) AF: 0.471 AC: 993 AN: 2108

Alfa AF: 0.467 Hom.: 78340

Bravo AF: 0.444

Asia WGS AF: 0.368 AC: 1276 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		1.4
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: rs4973768; hg19: chr3-27416013; COSMIC: COSV55394698; COSMIC: COSV55394698;