Variant 7-27128971-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002141.5(HOXA4):c.*254T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 562,430 control chromosomes in the GnomAD database, including 5,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2635 hom., cov: 34)

Exomes 𝑓: 0.10 ( 2773 hom. )

Consequence

HOXA4
NM_002141.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-27128971-A-G is Benign according to our data. Variant chr7-27128971-A-G is described in ClinVar as [Benign]. Clinvar id is 1270022.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 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.*254T>C		3_prime_UTR_variant	2/2	ENST00000360046.10	NP_002132.3	Q00056
HOXA3	NM_153631.3 linkuse as main transcript	c.-389-1901T>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.*254T>C		3_prime_UTR_variant	2/2	1	NM_002141.5	ENSP00000353151.5		Q00056
HOXA3	ENST00000612286.5 linkuse as main transcript	c.-389-1901T>C		intron_variant		2	NM_153631.3	ENSP00000484411.1		O43365

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24326

AN:

152124

Hom.:

2625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.104

AC:

42496

AN:

410188

Hom.:

2773

Cov.:

AF XY:

0.0998

AC XY:

21564

AN XY:

216150

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.0595

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.0658

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0881

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.160

AC:

24381

AN:

152242

Hom.:

2635

Cov.:

AF XY:

0.160

AC XY:

11931

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.0637

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.0707

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.109

Hom.:

1472

Bravo

AF:

0.175

Asia WGS

AF:

0.118

AC:

412

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.9

DANN

Benign

0.61

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