Genetic Variant SLC12A7:c.3160+68G>C (chr5-1053281-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.649

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A7	NM_006598.3 link	c.3160+68G>C		intron_variant	Intron 23 of 23	ENST00000264930.10	NP_006589.2	Q9Y666-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A7	ENST00000264930.10 link	c.3160+68G>C		intron_variant	Intron 23 of 23	1	NM_006598.3	ENSP00000264930.5		Q9Y666-1
SLC12A7	ENST00000634447.1 link	c.2875+68G>C		intron_variant	Intron 22 of 22	5		ENSP00000489285.1		A0A0U1RR18

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57684

AN:

152110

Hom.:

12858

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.373

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.502

Gnomad4 OTH exome

AF:

0.454

GnomAD4 genome

AF:

0.379

AC:

57680

AN:

152228

Hom.:

12853

Cov.:

AF XY:

0.378

AC XY:

28123

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.401

Gnomad4 ASJ

AF:

0.406

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.441

Hom.:

2069

Bravo

AF:

0.360

Asia WGS

AF:

0.385

AC:

1338

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.90

CADD

Benign

1.7

DANN

Benign

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over