20-46022179-A-G

Variant names:

• chr20-46022179-A-G
• rs6130997
• NM_001134771.2:c.121+293A>G

Variant summary

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

The NM_001134771.2(SLC12A5):​c.121+293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 266,798 control chromosomes in the GnomAD database, including 30,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18050 hom., cov: 23)
  • Exomes 𝑓: 0.42 (12169 hom.)
• Consequence: SLC12A5 NM_001134771.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270
• Publications: 8 publications found

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-46022179-A-G is Benign according to our data. Variant chr20-46022179-A-G is described in ClinVar as Benign. ClinVar VariationId is 1183011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134771.2. 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
	SLC12A5	NM_001134771.2		c.121+293A>G		intron	N/A	NP_001128243.1	Q9H2X9-1
	SLC12A5-AS1	NR_147699.1		n.-106T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	ENST00000454036.6	TSL:5	c.121+293A>G		intron	N/A	ENSP00000387694.1	Q9H2X9-1
	SLC12A5	ENST00000626701.1	TSL:3	c.121+293A>G		intron	N/A	ENSP00000487372.1	A0A0D9SGD0
	SLC12A5	ENST00000413737.2	TSL:3	c.46+293A>G		intron	N/A	ENSP00000487291.1	A0A0D9SGA5

Frequencies

GnomAD3 genomes AF: 0.490 AC: 72323 AN: 147582 Hom.: 18038 Cov.: 23

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.421 AC: 50116 AN: 119098 Hom.: 12169 AF XY: 0.423 AC XY: 26104 AN XY: 61762

African (AFR) AF: 0.507 AC: 1485 AN: 2930

American (AMR) AF: 0.386 AC: 1228 AN: 3178

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1751 AN: 4238

East Asian (EAS) AF: 0.710 AC: 5282 AN: 7440

South Asian (SAS) AF: 0.495 AC: 4774 AN: 9640

European-Finnish (FIN) AF: 0.384 AC: 3074 AN: 8002

Middle Eastern (MID) AF: 0.311 AC: 190 AN: 610

European-Non Finnish (NFE) AF: 0.386 AC: 29173 AN: 75500

Other (OTH) AF: 0.418 AC: 3159 AN: 7560

GnomAD4 genome AF: 0.490 AC: 72375 AN: 147700 Hom.: 18050 Cov.: 23 AF XY: 0.495 AC XY: 35559 AN XY: 71834

African (AFR) AF: 0.553 AC: 21814 AN: 39446

American (AMR) AF: 0.441 AC: 6581 AN: 14938

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1575 AN: 3460

East Asian (EAS) AF: 0.762 AC: 3763 AN: 4936

South Asian (SAS) AF: 0.596 AC: 2718 AN: 4558

European-Finnish (FIN) AF: 0.457 AC: 4595 AN: 10064

Middle Eastern (MID) AF: 0.392 AC: 113 AN: 288

European-Non Finnish (NFE) AF: 0.444 AC: 29806 AN: 67068

Other (OTH) AF: 0.450 AC: 918 AN: 2042

Alfa AF: 0.351 Hom.: 951

Bravo AF: 0.493

Asia WGS AF: 0.598 AC: 2072 AN: 3466

ClinVar

ClinVar submissions as Germline

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	-0.86
CADD	Benign	6.2
DANN	Benign	0.52
PhyloP100		-0.027
PromoterAI		-0.042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6130997; hg19: chr20-44650818;