Variant chr7-27129474-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002141.5(HOXA4):c.714A>C(p.Arg238Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 1,614,150 control chromosomes in the GnomAD database, including 752,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.95 ( 68778 hom., cov: 32)

Exomes 𝑓: 0.97 ( 683454 hom. )

Consequence

HOXA4
NM_002141.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0680

Variant links:

Genes affected

HOXA4 (HGNC:5105): (homeobox A4) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. [provided by RefSeq, Jul 2008]

HOXA4 links:

HOXA3 (HGNC:5104): (homeobox A3) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA3 links:

ENSG00000273433 (HGNC:):

ENSG00000273433 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 7-27129474-T-G is Benign according to our data. Variant chr7-27129474-T-G is described in ClinVar as [Benign]. Clinvar id is 1256657.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.068 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA4	NM_002141.5 linkuse as main transcript	c.714A>C	p.Arg238Arg	synonymous_variant	2/2	ENST00000360046.10	NP_002132.3	Q00056
HOXA3	NM_153631.3 linkuse as main transcript	c.-389-2404A>C		intron_variant		ENST00000612286.5	NP_705895.1	O43365A4D182A0A024RA33B3KPN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA4	ENST00000360046.10 linkuse as main transcript	c.714A>C	p.Arg238Arg	synonymous_variant	2/2	1	NM_002141.5	ENSP00000353151.5		Q00056
HOXA3	ENST00000612286.5 linkuse as main transcript	c.-389-2404A>C		intron_variant		2	NM_153631.3	ENSP00000484411.1		O43365

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

144517

AN:

152144

Hom.:

68720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

0.967

Gnomad AMR

AF:

0.967

Gnomad ASJ

AF:

0.982

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.944

Gnomad FIN

AF:

0.957

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.970

Gnomad OTH

AF:

0.946

GnomAD3 exomes

AF:

0.963

AC:

242253

AN:

251486

Hom.:

116753

AF XY:

0.962

AC XY:

130807

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.902

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.977

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.939

Gnomad FIN exome

AF:

0.958

Gnomad NFE exome

AF:

0.970

Gnomad OTH exome

AF:

0.964

GnomAD4 exome

AF:

0.967

AC:

1413401

AN:

1461888

Hom.:

683454

Cov.:

AF XY:

0.966

AC XY:

702352

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.899

Gnomad4 AMR exome

AF:

0.972

Gnomad4 ASJ exome

AF:

0.979

Gnomad4 EAS exome

AF:

0.997

Gnomad4 SAS exome

AF:

0.937

Gnomad4 FIN exome

AF:

0.961

Gnomad4 NFE exome

AF:

0.970

Gnomad4 OTH exome

AF:

0.964

GnomAD4 genome

AF:

0.950

AC:

144635

AN:

152262

Hom.:

68778

Cov.:

AF XY:

0.949

AC XY:

70625

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.901

Gnomad4 AMR

AF:

0.967

Gnomad4 ASJ

AF:

0.982

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.945

Gnomad4 FIN

AF:

0.957

Gnomad4 NFE

AF:

0.970

Gnomad4 OTH

AF:

0.947

Alfa

AF:

0.963

Hom.:

44066

Bravo

AF:

0.948

Asia WGS

AF:

0.968

AC:

3368

AN:

3478

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

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.2

DANN

Benign

0.79

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