5-1060251-C-G

Variant names:

• chr5-1060251-C-G
• rs4975699
• NM_006598.3:c.2847+93G>C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006598.3(SLC12A7):​c.2847+93G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 954,436 control chromosomes in the GnomAD database, including 394,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (50357 hom., cov: 34)
  • Exomes 𝑓: 0.92 (343777 hom.)
• Consequence: SLC12A7 NM_006598.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.208

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-1060251-C-G is Benign according to our data. Variant chr5-1060251-C-G is described in ClinVar as [Benign]. Clinvar id is 1268040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A7	NM_006598.3	c.2847+93G>C		intron_variant	Intron 21 of 23	ENST00000264930.10	NP_006589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A7	ENST00000264930.10	c.2847+93G>C		intron_variant	Intron 21 of 23	1	NM_006598.3	ENSP00000264930.5
SLC12A7	ENST00000634447.1	c.2547+93G>C		intron_variant	Intron 19 of 22	5		ENSP00000489285.1
SLC12A7	ENST00000513223.2	c.942+93G>C		intron_variant	Intron 7 of 7	5		ENSP00000428854.2
SLC12A7	ENST00000514994.1	n.147+93G>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116988 AN: 152118 Hom.: 50351 Cov.: 34

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.920 AC: 738303 AN: 802200 Hom.: 343777 AF XY: 0.923 AC XY: 388597 AN XY: 420952

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.936

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.957

Gnomad4 SAS exome AF: 0.934

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.939

Gnomad4 OTH exome AF: 0.895

GnomAD4 genome AF: 0.769 AC: 117012 AN: 152236 Hom.: 50357 Cov.: 34 AF XY: 0.776 AC XY: 57744 AN XY: 74440

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.818

Alfa AF: 0.777 Hom.: 3322

Bravo AF: 0.744

Asia WGS AF: 0.895 AC: 3110 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4975699; hg19: chr5-1060366;