rs2241603

Variant names:

• chr5-1053281-C-G
• rs2241603
• NM_006598.3:c.3160+68G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-1053281-C-G
• chr5-1053281-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006598.3(SLC12A7):​c.3160+68G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,556,148 control chromosomes in the GnomAD database, including 178,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12853 hom., cov: 35)
  • Exomes 𝑓: 0.48 (165941 hom.)
• Consequence: SLC12A7 NM_006598.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.649
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-1053281-C-G is Benign according to our data. Variant chr5-1053281-C-G is described in ClinVar as Benign. ClinVar VariationId is 1240420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 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.3160+68G>C		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.3160+68G>C		intron	N/A	ENSP00000264930.5	Q9Y666-1
	SLC12A7	ENST00000634447.1	TSL:5	c.2875+68G>C		intron	N/A	ENSP00000489285.1	A0A0U1RR18
	SLC12A7	ENST00000945163.1		c.3277+68G>C		intron	N/A	ENSP00000615222.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57684 AN: 152110 Hom.: 12858 Cov.: 35

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.482 AC: 676087 AN: 1403920 Hom.: 165941 AF XY: 0.483 AC XY: 334554 AN XY: 692394

African (AFR) AF: 0.111 AC: 3612 AN: 32542

American (AMR) AF: 0.431 AC: 17323 AN: 40176

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 8883 AN: 22382

East Asian (EAS) AF: 0.373 AC: 14540 AN: 38934

South Asian (SAS) AF: 0.484 AC: 36698 AN: 75830

European-Finnish (FIN) AF: 0.483 AC: 23701 AN: 49060

Middle Eastern (MID) AF: 0.410 AC: 2266 AN: 5530

European-Non Finnish (NFE) AF: 0.502 AC: 542688 AN: 1081402

Other (OTH) AF: 0.454 AC: 26376 AN: 58064

GnomAD4 genome AF: 0.379 AC: 57680 AN: 152228 Hom.: 12853 Cov.: 35 AF XY: 0.378 AC XY: 28123 AN XY: 74408

African (AFR) AF: 0.131 AC: 5445 AN: 41562

American (AMR) AF: 0.401 AC: 6132 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3472

East Asian (EAS) AF: 0.400 AC: 2066 AN: 5164

South Asian (SAS) AF: 0.483 AC: 2334 AN: 4828

European-Finnish (FIN) AF: 0.481 AC: 5096 AN: 10598

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 34004 AN: 67982

Other (OTH) AF: 0.372 AC: 786 AN: 2112

Alfa AF: 0.441 Hom.: 2069

Bravo AF: 0.360

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.65
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: rs2241603; hg19: chr5-1053396; COSMIC: COSV53756871; COSMIC: COSV53756871;