Genetic Variant NM_001321103.2:c.778+56C>T (chr3-27433860-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

10 publications found

Variant links:

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

SLC4A7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2 link	c.778+56C>T		intron_variant	Intron 6 of 25	ENST00000454389.6	NP_001308032.1	Q9Y6M7-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6 link	c.778+56C>T		intron_variant	Intron 6 of 25	1	NM_001321103.2	ENSP00000390394.1		Q9Y6M7-7

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19252

AN:

152030

Hom.:

1215

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6555

13110

19665

26220

32775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.127

AC:

19249

AN:

152150

Hom.:

1215

Cov.:

AF XY:

0.124

AC XY:

9248

AN XY:

74356

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8890

AN:

67996

Other (OTH)

AF:

0.135

AC:

284

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

872

1744

2617

3489

4361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.60

(source)

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)

(source)

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

Publications

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over