Genetic Variant ENST00000422059.5:n.647-120A>G (chr6-43997428-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000422059.5(SCIRT):n.647-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,092 control chromosomes in the GnomAD database, including 13,667 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 ( 13666 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

SCIRT
ENST00000422059.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

6 publications found

Variant links:

Genes affected

SCIRT (HGNC:55341): (stem cell inhibitory RNA transcript)

SCIRT links:

ENSG00000289609 (HGNC:):

ENSG00000289609 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=-0.57).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
SCIRT	NR_125864.1 link	n.647-120A>G	intron_variant	Intron 4 of 4
SCIRT	NR_125865.1 link	n.431-120A>G	intron_variant	Intron 3 of 3
LOC124901321	XR_007059591.1 link	n.43-1523T>C	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
SCIRT	ENST00000422059.5 link	n.647-120A>G	intron_variant	Intron 4 of 4	2
SCIRT	ENST00000607590.1 link	n.430-120A>G	intron_variant	Intron 3 of 3	3
SCIRT	ENST00000652850.2 link	n.520-120A>G	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52534

AN:

151902

Hom.:

13612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.320

GnomAD4 exome

AF:

0.153

AC:

AN:

Hom.:

AF XY:

0.196

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.182

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.158

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.346

AC:

52657

AN:

152020

Hom.:

13666

Cov.:

AF XY:

0.346

AC XY:

25698

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.726

AC:

30089

AN:

41436

American (AMR)

AF:

0.282

AC:

4307

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1083

AN:

3472

East Asian (EAS)

AF:

0.394

AC:

2035

AN:

5160

South Asian (SAS)

AF:

0.348

AC:

1675

AN:

4816

European-Finnish (FIN)

AF:

0.153

AC:

1618

AN:

10572

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10929

AN:

67964

Other (OTH)

AF:

0.324

AC:

684

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1308

2615

3923

5230

6538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.229

Hom.:

18728

Bravo

AF:

0.373

Asia WGS

AF:

0.416

AC:

1449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.7

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