Variant 5-75669267-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001276713.2(ANKDD1B):c.1409G>A(p.Arg470His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 1,232,134 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 27 hom. )

Consequence

ANKDD1B
NM_001276713.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ANKDD1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006200969).

BP6

Variant 5-75669267-G-A is Benign according to our data. Variant chr5-75669267-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2 linkuse as main transcript	c.1409G>A	p.Arg470His	missense_variant	13/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4 linkuse as main transcript	c.1409G>A	p.Arg470His	missense_variant	13/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

588

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00583

AC:

AN:

8400

Hom.:

AF XY:

0.00520

AC XY:

AN XY:

4038

show subpopulations

Gnomad AFR exome

AF:

0.00286

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00320

Gnomad NFE exome

AF:

0.00670

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00673

AC:

7268

AN:

1079806

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

3407

AN XY:

509776

show subpopulations

Gnomad4 AFR exome

AF:

0.000697

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00577

Gnomad4 EAS exome

AF:

0.0000377

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.00209

Gnomad4 NFE exome

AF:

0.00739

Gnomad4 OTH exome

AF:

0.00609

GnomAD4 genome

AF:

0.00385

AC:

587

AN:

152328

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

270

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00628

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.00399

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00727

AC:

ExAC

AF:

0.00190

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	ANKDD1B: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.060

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0062

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.26

Sift4G

Benign

0.13

Vest4

0.078

MVP

0.75

GERP RS

0.36

Varity_R

0.042

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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