5-1057845-C-T

Variant names:

• chr5-1057845-C-T
• rs35791340
• NM_006598.3:c.2848-196G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006598.3(SLC12A7):​c.2848-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,086 control chromosomes in the GnomAD database, including 37,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (37381 hom., cov: 32)
• Consequence: SLC12A7 NM_006598.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.370
• Publications: 2 publications found

Genes affected

SLC12A7 (HGNC:10915): (solute carrier family 12 member 7) Enables protein kinase binding activity. Predicted to be involved in several processes, including cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A7 Gene-Disease associations (from GenCC):

• renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-1057845-C-T is Benign according to our data. Variant chr5-1057845-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006598.3. 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
	SLC12A7	NM_006598.3	MANE Select	c.2848-196G>A		intron	N/A	NP_006589.2	Q9Y666-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A7	ENST00000264930.10	TSL:1 MANE Select	c.2848-196G>A		intron	N/A	ENSP00000264930.5	Q9Y666-1
	SLC12A7	ENST00000634447.1	TSL:5	c.2548-196G>A		intron	N/A	ENSP00000489285.1	A0A0U1RR18
	SLC12A7	ENST00000945163.1		c.2950-196G>A		intron	N/A	ENSP00000615222.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100700 AN: 151968 Hom.: 37384 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.688

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100707 AN: 152086 Hom.: 37381 Cov.: 32 AF XY: 0.667 AC XY: 49562 AN XY: 74350

African (AFR) AF: 0.292 AC: 12104 AN: 41482

American (AMR) AF: 0.742 AC: 11345 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2772 AN: 3470

East Asian (EAS) AF: 0.776 AC: 3997 AN: 5154

South Asian (SAS) AF: 0.800 AC: 3856 AN: 4818

European-Finnish (FIN) AF: 0.825 AC: 8743 AN: 10598

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55520 AN: 67968

Other (OTH) AF: 0.683 AC: 1441 AN: 2110

Alfa AF: 0.753 Hom.: 7717

Bravo AF: 0.637

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		0.37
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1
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: rs35791340; hg19: chr5-1057960;