Variant 9-38575535-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_147195.4(ANKRD18A):c.2905A>G(p.Ile969Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,551,628 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 41 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 40 hom. )

Consequence

ANKRD18A
NM_147195.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.91

Variant links:

Genes affected

ANKRD18A (HGNC:23643): (ankyrin repeat domain 18A)

ANKRD18A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003167659).

BP6

Variant 9-38575535-T-C is Benign according to our data. Variant chr9-38575535-T-C is described in ClinVar as [Benign]. Clinvar id is 775273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1974/152336) while in subpopulation AFR AF= 0.0451 (1874/41578). AF 95% confidence interval is 0.0434. There are 41 homozygotes in gnomad4. There are 890 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD18A	NM_147195.4 linkuse as main transcript	c.2905A>G	p.Ile969Val	missense_variant	15/16	ENST00000399703.6	NP_671728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD18A	ENST00000399703.6 linkuse as main transcript	c.2905A>G	p.Ile969Val	missense_variant	15/16	1	NM_147195.4	ENSP00000382610	A2	Q8IVF6-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1959

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00281

AC:

442

AN:

157024

Hom.:

AF XY:

0.00216

AC XY:

179

AN XY:

83010

show subpopulations

Gnomad AFR exome

AF:

0.0443

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000313

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00142

AC:

1985

AN:

1399292

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

885

AN XY:

690162

show subpopulations

Gnomad4 AFR exome

AF:

0.0484

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.0130

AC:

1974

AN:

152336

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

890

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0451

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00712

Hom.:

Bravo

AF:

0.0147

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0535

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00487

AC:

120

Asia WGS

AF:

0.00376

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0020

DANN

Benign

0.15

DEOGEN2

Benign

0.0013

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.29

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.29

.;N

REVEL

Benign

0.025

Sift

Benign

0.40

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.047

.;B

Vest4

0.011

MVP

0.040

MPC

0.025

ClinPred

0.00020

GERP RS

-2.8

Varity_R

0.031

gMVP

0.0071

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