Genetic Variant ANKHD1-DT:n.154T>G (chr5-140401510-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000507521.3(ANKHD1-DT):n.154T>G 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 0.182 in 158,782 control chromosomes in the GnomAD database, including 3,408 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 0.18 ( 3236 hom., cov: 32)

Exomes 𝑓: 0.21 ( 172 hom. )

Consequence

ANKHD1-DT
ENST00000507521.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

5 publications found

Variant links:

Genes affected

ANKHD1-DT (HGNC:55564): (ANKHD1 divergent transcript)

ANKHD1-DT links:

ANKHD1 (HGNC:24714): (ankyrin repeat and KH domain containing 1) This gene encodes a protein with multiple ankyrin repeat domains and a single KH-domain. The protein is thought to function as a scaffolding protein, and it may be involved in the regulation of caspases and thereby play an antiapoptotic role in cell survival. Alternative splicing results in multiple transcript variants, one of which generates a fusion transcript (MASK-BP3) with the downstream eIF4E-binding protein 3 (EIF4EBP3) gene, resulting in a protein comprised of the ANKHD1 sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Sep 2010]

ANKHD1 links:

ENSG00000302458 (HGNC:):

ENSG00000302458 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=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000507521.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
ANKHD1-DT	NR_186044.1	n.-109T>G	upstream_gene	N/A
ANKHD1-DT	NR_186045.1	n.-109T>G	upstream_gene	N/A
ANKHD1-DT	NR_186046.1	n.-109T>G	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ANKHD1-DT	ENST00000507521.3	TSL:2	n.154T>G	non_coding_transcript_exon	Exon 1 of 2
ANKHD1-DT	ENST00000687631.3		n.183T>G	non_coding_transcript_exon	Exon 1 of 1
ANKHD1-DT	ENST00000786872.1		n.197T>G	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27549

AN:

152140

Hom.:

3227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0441

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.215

AC:

1401

AN:

6524

Hom.:

172

AF XY:

0.223

AC XY:

794

AN XY:

3568

show subpopulations

African (AFR)

AF:

0.0714

AC:

AN:

238

American (AMR)

AF:

0.183

AC:

AN:

180

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

AN:

270

East Asian (EAS)

AF:

0.292

AC:

AN:

178

South Asian (SAS)

AF:

0.239

AC:

200

AN:

836

European-Finnish (FIN)

AF:

0.285

AC:

AN:

200

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.216

AC:

913

AN:

4224

Other (OTH)

AF:

0.178

AC:

AN:

382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.181

AC:

27565

AN:

152258

Hom.:

3236

Cov.:

AF XY:

0.184

AC XY:

13674

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0439

AC:

1826

AN:

41576

American (AMR)

AF:

0.211

AC:

3231

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

685

AN:

3472

East Asian (EAS)

AF:

0.290

AC:

1500

AN:

5176

South Asian (SAS)

AF:

0.266

AC:

1284

AN:

4830

European-Finnish (FIN)

AF:

0.267

AC:

2825

AN:

10594

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15720

AN:

68008

Other (OTH)

AF:

0.187

AC:

396

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1112

2225

3337

4450

5562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.177

Hom.:

1156

Bravo

AF:

0.169

Asia WGS

AF:

0.284

AC:

989

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

-0.048

PromoterAI

-0.018

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over