chr3-27394730-C-T

Variant names:

• chr3-27394730-C-T
• rs545807896
• NM_001321103.2:c.2905G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001321103.2(SLC4A7):​c.2905G>A​(p.Val969Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,614,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000042 (1 hom.)
• Consequence: SLC4A7 NM_001321103.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.692
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023766696).
• BP6: Variant 3-27394730-C-T is Benign according to our data. Variant chr3-27394730-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2374916.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2905G>A	p.Val969Ile	missense	Exon 20 of 26	NP_001308032.1	Q9Y6M7-7
	SLC4A7	NM_001321104.2		c.2866G>A	p.Val956Ile	missense	Exon 20 of 26	NP_001308033.1	Q9Y6M7-8
	SLC4A7	NM_003615.5		c.2878G>A	p.Val960Ile	missense	Exon 20 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.2905G>A	p.Val969Ile	missense	Exon 20 of 26	ENSP00000390394.1	Q9Y6M7-7
	SLC4A7	ENST00000440156.5	TSL:1	c.2866G>A	p.Val956Ile	missense	Exon 20 of 26	ENSP00000414797.1	Q9Y6M7-8
	SLC4A7	ENST00000295736.9	TSL:1	c.2878G>A	p.Val960Ile	missense	Exon 20 of 25	ENSP00000295736.5	Q9Y6M7-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251218 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1461852 Hom.: 1 Cov.: 31 AF XY: 0.0000523 AC XY: 38 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111988

Other (OTH) AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.65
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.69
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.19
Sift	Benign	0.84	T
Sift4G	Benign	0.79	T
Polyphen		0.026	B
Vest4		0.14
MVP		0.068
MPC		0.25
ClinPred		0.014	T
GERP RS		4.0
Varity_R		0.013
gMVP		0.23
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs545807896; hg19: chr3-27436221; COSMIC: COSV99840500; COSMIC: COSV99840500;