Variant 12-85280309-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000316824.4(ALX1):c.48A>G(p.Lys16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,746 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 32)

Exomes 𝑓: 0.015 ( 168 hom. )

Consequence

ALX1
ENST00000316824.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.93

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-85280309-A-G is Benign according to our data. Variant chr12-85280309-A-G is described in ClinVar as [Benign]. Clinvar id is 2038190.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.93 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1682/152212) while in subpopulation NFE AF= 0.016 (1086/68016). AF 95% confidence interval is 0.0152. There are 13 homozygotes in gnomad4. There are 807 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALX1	NM_006982.3 linkuse as main transcript	c.48A>G	p.Lys16=	synonymous_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.48A>G	p.Lys16=	synonymous_variant	1/4	1	NM_006982.3	ENSP00000315417	P1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1684

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0119

AC:

2991

AN:

250978

Hom.:

AF XY:

0.0125

AC XY:

1692

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00590

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0147

AC:

21477

AN:

1461534

Hom.:

168

Cov.:

AF XY:

0.0148

AC XY:

10750

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00622

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0131

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0111

AC:

1682

AN:

152212

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

807

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0214

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.00979

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0144

EpiControl

AF:

0.0154

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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