NM_001321103.2:c.778+56C>T

Variant names:

• chr3-27433860-G-A
• rs3278
• NM_001321103.2:c.778+56C>T

Variant summary

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

The NM_001321103.2(SLC4A7):​c.778+56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,413,372 control chromosomes in the GnomAD database, including 10,596 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 0.13 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9381 hom.)
• Consequence: SLC4A7 NM_001321103.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 10 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 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.778+56C>T		intron	N/A	NP_001308032.1
	SLC4A7	NM_001321104.2		c.739+95C>T		intron	N/A	NP_001308033.1
	SLC4A7	NM_003615.5		c.751+56C>T		intron	N/A	NP_003606.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A7	ENST00000454389.6	TSL:1 MANE Select	c.778+56C>T		intron	N/A	ENSP00000390394.1
	SLC4A7	ENST00000440156.5	TSL:1	c.739+95C>T		intron	N/A	ENSP00000414797.1
	SLC4A7	ENST00000295736.9	TSL:1	c.751+56C>T		intron	N/A	ENSP00000295736.5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19252 AN: 152030 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.118 AC: 148218 AN: 1261222 Hom.: 9381 AF XY: 0.116 AC XY: 73700 AN XY: 638018

African (AFR) AF: 0.143 AC: 4153 AN: 29098

American (AMR) AF: 0.0952 AC: 4102 AN: 43102

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4024 AN: 24812

East Asian (EAS) AF: 0.0626 AC: 2421 AN: 38698

South Asian (SAS) AF: 0.0423 AC: 3433 AN: 81106

European-Finnish (FIN) AF: 0.0985 AC: 5225 AN: 53054

Middle Eastern (MID) AF: 0.204 AC: 1093 AN: 5362

European-Non Finnish (NFE) AF: 0.126 AC: 117028 AN: 932360

Other (OTH) AF: 0.126 AC: 6739 AN: 53630

GnomAD4 genome AF: 0.127 AC: 19249 AN: 152150 Hom.: 1215 Cov.: 32 AF XY: 0.124 AC XY: 9248 AN XY: 74356

African (AFR) AF: 0.142 AC: 5914 AN: 41528

American (AMR) AF: 0.120 AC: 1831 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3472

East Asian (EAS) AF: 0.0537 AC: 277 AN: 5160

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4826

European-Finnish (FIN) AF: 0.0984 AC: 1040 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8890 AN: 67996

Other (OTH) AF: 0.135 AC: 284 AN: 2106

Alfa AF: 0.134 Hom.: 2626

Bravo AF: 0.130

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.60
DANN	Benign	0.59
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3278; hg19: chr3-27475351; COSMIC: COSV55402522;