dbSNP rs2664588: ENSG00000234967:n.260C>T (chr20-47951890-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 ENST00000431915.1(ENSG00000234967):n.260C>T 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 0.346 in 152,166 control chromosomes in the GnomAD database, including 11,031 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 0.35 ( 11030 hom., cov: 32)

Exomes 𝑓: 0.21 ( 1 hom. )

Consequence

ENSG00000234967
ENST00000431915.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Publications

5 publications found

Variant links:

Genes affected

ENSG00000234967 (HGNC:):

ENSG00000234967 links:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105372637	XR_936787.2 link	n.204+45C>T	intron_variant	Intron 2 of 5
LOC105372637	XR_936788.2 link	n.204+45C>T	intron_variant	Intron 2 of 5
LOC105372637	XR_936789.2 link	n.204+45C>T	intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000234967	ENST00000431915.1 link	n.260C>T	non_coding_transcript_exon_variant	Exon 2 of 2	2
ENSG00000234967	ENST00000666669.1 link	n.262C>T	non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000234967	ENST00000416646.2 link	n.140+45C>T	intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52705

AN:

151942

Hom.:

11035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.506

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.369

GnomAD4 exome

AF:

0.208

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.197

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.156

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00111084), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.347

AC:

52699

AN:

152060

Hom.:

11030

Cov.:

AF XY:

0.349

AC XY:

25959

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.112

AC:

4646

AN:

41482

American (AMR)

AF:

0.452

AC:

6910

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

1713

AN:

3466

East Asian (EAS)

AF:

0.109

AC:

565

AN:

5172

South Asian (SAS)

AF:

0.388

AC:

1874

AN:

4824

European-Finnish (FIN)

AF:

0.506

AC:

5349

AN:

10566

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30292

AN:

67952

Other (OTH)

AF:

0.364

AC:

769

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1567

3134

4700

6267

7834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.427

Hom.:

12562

Bravo

AF:

0.332

Asia WGS

AF:

0.225

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.55

(source)

DANN

Benign

0.35

PhyloP100

-2.1

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