chr21-37618141-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002240.5(KCNJ6):​c.*7018C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,222 control chromosomes in the GnomAD database, including 6,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6903 hom., cov: 33)
Exomes 𝑓: 0.30 ( 5 hom. )

Consequence

KCNJ6
NM_002240.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129
Variant links:
Genes affected
KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNJ6NM_002240.5 linkuse as main transcriptc.*7018C>T 3_prime_UTR_variant 4/4 ENST00000609713.2
KCNJ6-AS1NR_183540.1 linkuse as main transcriptn.408-80414G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNJ6ENST00000609713.2 linkuse as main transcriptc.*7018C>T 3_prime_UTR_variant 4/41 NM_002240.5 P1
ENST00000667151.1 linkuse as main transcriptn.160+24005G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.294
AC:
44724
AN:
152034
Hom.:
6893
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.265
Gnomad AMI
AF:
0.508
Gnomad AMR
AF:
0.233
Gnomad ASJ
AF:
0.308
Gnomad EAS
AF:
0.135
Gnomad SAS
AF:
0.337
Gnomad FIN
AF:
0.365
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.320
Gnomad OTH
AF:
0.295
GnomAD4 exome
AF:
0.300
AC:
21
AN:
70
Hom.:
5
Cov.:
0
AF XY:
0.308
AC XY:
16
AN XY:
52
show subpopulations
Gnomad4 AFR exome
AF:
0.500
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.323
GnomAD4 genome
AF:
0.294
AC:
44767
AN:
152152
Hom.:
6903
Cov.:
33
AF XY:
0.295
AC XY:
21974
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.265
Gnomad4 AMR
AF:
0.233
Gnomad4 ASJ
AF:
0.308
Gnomad4 EAS
AF:
0.135
Gnomad4 SAS
AF:
0.338
Gnomad4 FIN
AF:
0.365
Gnomad4 NFE
AF:
0.320
Gnomad4 OTH
AF:
0.291
Alfa
AF:
0.315
Hom.:
7690
Bravo
AF:
0.284
Asia WGS
AF:
0.197
AC:
691
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
5.3
DANN
Benign
0.51

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.

Other links and lift over

dbSNP: rs2835837; hg19: chr21-38990443; API