Variant 5-140507254-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000360839.7(ANKHD1):c.3551+277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,084 control chromosomes in the GnomAD database, including 34,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 34539 hom., cov: 32)

Consequence

ANKHD1
ENST00000360839.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.62

Variant links:

Genes affected

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:

ANKHD1-EIF4EBP3 (HGNC:33530): (ANKHD1-EIF4EBP3 readthrough) The ANKHD1-EIF4EBP3 mRNA is an infrequent but naturally occurring readthrough transcript of the neighboring ANKHD1 and EIF4EBP3 genes. This readthrough transcript encodes a protein composed mostly of the multiple ankyrin repeats, single KH-domain protein, with its C-terminus encoded in a different reading frame from the shared portion of the EIF4EBP3 gene. The significance of this readthrough mRNA and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2009]

ANKHD1-EIF4EBP3 links:

ANKHD1 (HGNC:):

ANKHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 5-140507254-A-G is Benign according to our data. Variant chr5-140507254-A-G is described in ClinVar as [Benign]. Clinvar id is 1228896.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKHD1	NM_017747.3 linkuse as main transcript	c.3551+277A>G		intron_variant		ENST00000360839.7	NP_060217.1	Q8IWZ3-1
ANKHD1-EIF4EBP3	NM_020690.6 linkuse as main transcript	c.3551+277A>G		intron_variant			NP_065741.3	Q8IWZ3-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKHD1	ENST00000360839.7 linkuse as main transcript	c.3551+277A>G		intron_variant		1	NM_017747.3	ENSP00000354085.2		Q8IWZ3-1
ANKHD1-EIF4EBP3	ENST00000532219.5 linkuse as main transcript	c.3551+277A>G		intron_variant		2		ENSP00000432016.1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101739

AN:

151966

Hom.:

34520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.669

AC:

101815

AN:

152084

Hom.:

34539

Cov.:

AF XY:

0.668

AC XY:

49633

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.585

Gnomad4 AMR

AF:

0.694

Gnomad4 ASJ

AF:

0.660

Gnomad4 EAS

AF:

0.841

Gnomad4 SAS

AF:

0.752

Gnomad4 FIN

AF:

0.636

Gnomad4 NFE

AF:

0.700

Gnomad4 OTH

AF:

0.682

Alfa

AF:

0.650

Hom.:

5192

Bravo

AF:

0.671

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.087

DANN

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over