Genetic Variant XR_007066682.1:n.1548G>A (chr1-159999218-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_007066682.1(LOC124904436):n.1548G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 384,180 control chromosomes in the GnomAD database, including 8,637 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 0.22 ( 4009 hom., cov: 31)

Exomes 𝑓: 0.19 ( 4628 hom. )

Consequence

LOC124904436
XR_007066682.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

Publications

6 publications found

Variant links:

Genes affected

LOC124904436 (HGNC:):

LOC124904436 links:

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

KCNJ10 links:

LINC01133 (HGNC:49447): (long intergenic non-protein coding RNA 1133)

LINC01133 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904436	XR_007066682.1 link	n.1548G>A		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
KCNJ10	ENST00000639408.2 link	c.*240G>A	3_prime_UTR_variant	Exon 4 of 4	5	ENSP00000491635.1	A0A1W2PQC0
KCNJ10	ENST00000637644.1 link	c.*251G>A	3_prime_UTR_variant	Exon 3 of 3	5	ENSP00000490282.1	A0A1B0GUX2
KCNJ10	ENST00000640914.1 link	c.*308G>A	3_prime_UTR_variant	Exon 3 of 3	5	ENSP00000491175.1	A0A1W2PP61

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33532

AN:

151844

Hom.:

4010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.0633

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.192

AC:

44676

AN:

232218

Hom.:

4628

Cov.:

AF XY:

0.191

AC XY:

22549

AN XY:

117886

show subpopulations

African (AFR)

AF:

0.258

AC:

1770

AN:

6864

American (AMR)

AF:

0.292

AC:

2043

AN:

7006

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

2543

AN:

8906

East Asian (EAS)

AF:

0.0497

AC:

1093

AN:

21972

South Asian (SAS)

AF:

0.130

AC:

270

AN:

2076

European-Finnish (FIN)

AF:

0.185

AC:

3519

AN:

19072

Middle Eastern (MID)

AF:

0.212

AC:

258

AN:

1216

European-Non Finnish (NFE)

AF:

0.201

AC:

30042

AN:

149638

Other (OTH)

AF:

0.203

AC:

3138

AN:

15468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1628

3257

4885

6514

8142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.221

AC:

33548

AN:

151962

Hom.:

4009

Cov.:

AF XY:

0.222

AC XY:

16476

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.263

AC:

10897

AN:

41400

American (AMR)

AF:

0.291

AC:

4439

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1060

AN:

3468

East Asian (EAS)

AF:

0.0638

AC:

330

AN:

5170

South Asian (SAS)

AF:

0.143

AC:

687

AN:

4814

European-Finnish (FIN)

AF:

0.182

AC:

1923

AN:

10580

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.200

AC:

13614

AN:

67948

Other (OTH)

AF:

0.206

AC:

433

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1279

2558

3838

5117

6396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

6226

Bravo

AF:

0.234

Asia WGS

AF:

0.128

AC:

444

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.47

PhyloP100

-0.45

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over