11-128838623-C-CTTG

Position:

• chr11-128838623-C-CTTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153766.3(KCNJ1):​c.*499_*501dupCAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 160,464 control chromosomes in the GnomAD database, including 2,142 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2033 hom., cov: 29)
  • Exomes 𝑓: 0.13 (109 hom.)
• Consequence: KCNJ1 NM_153766.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

Genes affected

KCNJ1 (HGNC:6255): (potassium inwardly rectifying channel subfamily J member 1) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-128838623-C-CTTG is Benign according to our data. Variant chr11-128838623-C-CTTG is described in ClinVar as [Benign]. Clinvar id is 303561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ1	NM_153766.3	c.*499_*501dupCAA		3_prime_UTR_variant	3/3	ENST00000392666.6	NP_722450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ1	ENST00000392666	c.*499_*501dupCAA		3_prime_UTR_variant	3/3	1	NM_153766.3	ENSP00000376434.1
KCNJ1	ENST00000324036	c.*499_*501dupCAA		3_prime_UTR_variant	4/4	1		ENSP00000316233.3
KCNJ1	ENST00000392665	c.*499_*501dupCAA		3_prime_UTR_variant	2/2	1		ENSP00000376433.2
KCNJ1	ENST00000440599	c.*499_*501dupCAA		3_prime_UTR_variant	3/3	1		ENSP00000406320.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24429 AN: 151958 Hom.: 2025 Cov.: 29

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.127 AC: 1067 AN: 8388 Hom.: 109 Cov.: 0 AF XY: 0.131 AC XY: 593 AN XY: 4514

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.0729

Gnomad4 ASJ exome AF: 0.0577

Gnomad4 EAS exome AF: 0.0424

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.0721

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.161 AC: 24457 AN: 152076 Hom.: 2033 Cov.: 29 AF XY: 0.164 AC XY: 12156 AN XY: 74332

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.149

Alfa AF: 0.153 Hom.: 176

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Antenatal Bartter syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113008742; hg19: chr11-128708518;