Genetic Variant ENSG00000227370:n.19C>T (chr22-42132561-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 ENST00000417586.1(ENSG00000227370):n.19C>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 0.275 in 150,752 control chromosomes in the GnomAD database, including 7,283 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 0.27 ( 7274 hom., cov: 32)

Exomes 𝑓: 0.25 ( 9 hom. )

Consequence

ENSG00000227370
ENST00000417586.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.764

Publications

23 publications found

Variant links:

Genes affected

ENSG00000227370 (HGNC:):

ENSG00000227370 links:

NDUFA6-DT (HGNC:45273): (NDUFA6 divergent transcript)

NDUFA6-DT 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=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000227370	ENST00000417586.1 link	n.19C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
NDUFA6-DT	ENST00000617009.4 link	n.352C>T	non_coding_transcript_exon_variant	Exon 2 of 5	5
NDUFA6-DT	ENST00000621190.1 link	n.352C>T	non_coding_transcript_exon_variant	Exon 2 of 8	5
NDUFA6-DT	ENST00000439129.5 link	n.1719-3638C>T	intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41377

AN:

150466

Hom.:

7264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.250

AC:

AN:

172

Hom.:

Cov.:

AF XY:

0.234

AC XY:

AN XY:

128

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.297

AC:

AN:

118

Other (OTH)

AF:

0.0625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.275

AC:

41402

AN:

150580

Hom.:

7274

Cov.:

AF XY:

0.281

AC XY:

20631

AN XY:

73538

show subpopulations

African (AFR)

AF:

0.139

AC:

5666

AN:

40794

American (AMR)

AF:

0.300

AC:

4553

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1199

AN:

3462

East Asian (EAS)

AF:

0.148

AC:

755

AN:

5110

South Asian (SAS)

AF:

0.383

AC:

1819

AN:

4746

European-Finnish (FIN)

AF:

0.389

AC:

4087

AN:

10498

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.331

AC:

22357

AN:

67500

Other (OTH)

AF:

0.304

AC:

633

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1214

2428

3643

4857

6071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.268

Hom.:

2288

Bravo

AF:

0.261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

PhyloP100

-0.76

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