Variant chr12-85280443-A-G 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 ENST00000316824.4(ALX1):c.182A>G(p.His61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,612,180 control chromosomes in the GnomAD database, including 123 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 0.0076 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

ALX1
ENST00000316824.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

ALX1 (HGNC:1494): (ALX homeobox 1) The specific function of this gene has yet to be determined in humans; however, in rodents, it is necessary for survival of the forebrain mesenchyme and may also be involved in development of the cervix. Mutations in the mouse gene lead to neural tube defects such as acrania and meroanencephaly. [provided by RefSeq, Jul 2008]

ALX1 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=0.007940471).

BP6

Variant 12-85280443-A-G is Benign according to our data. Variant chr12-85280443-A-G is described in ClinVar as [Benign]. Clinvar id is 770412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-85280443-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALX1	NM_006982.3 linkuse as main transcript	c.182A>G	p.His61Arg	missense_variant	1/4	ENST00000316824.4	NP_008913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALX1	ENST00000316824.4 linkuse as main transcript	c.182A>G	p.His61Arg	missense_variant	1/4	1	NM_006982.3	ENSP00000315417	P1

Frequencies

GnomAD3 genomes

AF:

0.00760

AC:

1156

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00753

AC:

1882

AN:

250064

Hom.:

AF XY:

0.00767

AC XY:

1040

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00405

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.00982

GnomAD4 exome

AF:

0.0111

AC:

16180

AN:

1459914

Hom.:

118

Cov.:

AF XY:

0.0109

AC XY:

7897

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00496

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00410

Gnomad4 FIN exome

AF:

0.00369

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00759

AC:

1155

AN:

152266

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

530

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00793

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0110

AC:

ExAC

AF:

0.00721

AC:

875

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	ALX1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.11

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0079

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.1

REVEL

Benign

0.25

Sift

Benign

0.037

Sift4G

Benign

0.31

Polyphen

0.099

Vest4

0.48

MVP

0.74

MPC

0.45

ClinPred

0.031

GERP RS

5.5

Varity_R

0.23

gMVP

0.35

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