rs7310043

Variant names:

• chr12-21765468-A-T
• rs7310043
• NM_004982.4:c.*255T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-21765468-A-T
• chr12-21765468-A-G

Variant summary

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

The NM_004982.4(KCNJ8):​c.*255T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 527,194 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (312 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (92 hom.)
• Consequence: KCNJ8 NM_004982.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262
• Publications: 2 publications found

Genes affected

KCNJ8 (HGNC:6269): (potassium inwardly rectifying channel subfamily J member 8) 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. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins. Defects in this gene may be a cause of J-wave syndromes and sudden infant death syndrome (SIDS). [provided by RefSeq, May 2012]

KCNJ8 Gene-Disease associations (from GenCC):

• hypertrichotic osteochondrodysplasia Cantu type

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Brugada syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp
• Brugada syndrome 1

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNJ8-AS1 (HGNC:58193):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-21765468-A-T is Benign according to our data. Variant chr12-21765468-A-T is described in ClinVar as Benign. ClinVar VariationId is 1283823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004982.4. 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
	KCNJ8	NM_004982.4	MANE Select	c.*255T>A		3_prime_UTR	Exon 3 of 3	NP_004973.1	Q15842

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ8	ENST00000240662.3	TSL:1 MANE Select	c.*255T>A		3_prime_UTR	Exon 3 of 3	ENSP00000240662.2	Q15842
	KCNJ8	ENST00000859815.1		c.*255T>A		3_prime_UTR	Exon 4 of 4	ENSP00000529874.1
	KCNJ8	ENST00000951731.1		c.*255T>A		3_prime_UTR	Exon 5 of 5	ENSP00000621790.1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5206 AN: 152136 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0278

GnomAD4 exome AF: 0.00453 AC: 1698 AN: 374940 Hom.: 92 Cov.: 2 AF XY: 0.00385 AC XY: 766 AN XY: 198898

African (AFR) AF: 0.122 AC: 1306 AN: 10726

American (AMR) AF: 0.00772 AC: 125 AN: 16192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11324

East Asian (EAS) AF: 0.00 AC: 0 AN: 23968

South Asian (SAS) AF: 0.000163 AC: 7 AN: 43034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22482

Middle Eastern (MID) AF: 0.00309 AC: 5 AN: 1620

European-Non Finnish (NFE) AF: 0.000236 AC: 53 AN: 224148

Other (OTH) AF: 0.00942 AC: 202 AN: 21446

GnomAD4 genome AF: 0.0343 AC: 5221 AN: 152254 Hom.: 312 Cov.: 32 AF XY: 0.0337 AC XY: 2510 AN XY: 74446

African (AFR) AF: 0.119 AC: 4943 AN: 41526

American (AMR) AF: 0.0133 AC: 204 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68038

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.0393

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7310043; hg19: chr12-21918402;