Variant chr7-27093970-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_005522.5(HOXA1):c.*470T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00882 in 161,184 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 23 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

HOXA1
NM_005522.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.924

Variant links:

Genes affected

HOXA1 (HGNC:5099): (homeobox A1) 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. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region. [provided by RefSeq, Jul 2008]

HOXA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 7-27093970-A-T is Benign according to our data. Variant chr7-27093970-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 359948.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00928 (1414/152326) while in subpopulation AFR AF= 0.0316 (1314/41558). AF 95% confidence interval is 0.0302. There are 23 homozygotes in gnomad4. There are 667 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA1	NM_005522.5 link	c.*470T>A		3_prime_UTR_variant	2/2	ENST00000643460.2	NP_005513.2	P49639
HOXA1	NM_153620.3 link	c.*861T>A		3_prime_UTR_variant	3/3		NP_705873.3	P49639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460 link	c.*470T>A		3_prime_UTR_variant	2/2		NM_005522.5	ENSP00000494260.2		A0A2R8Y4R9
HOXA1	ENST00000355633 link	c.*861T>A		3_prime_UTR_variant	3/3	1		ENSP00000347851.5		E7ERT8

Frequencies

GnomAD3 genomes

AF:

0.00921

AC:

1402

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000558

Gnomad OTH

AF:

0.00670

GnomAD4 exome

AF:

0.000903

AC:

AN:

8858

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

4654

show subpopulations

Gnomad4 AFR exome

AF:

0.0426

Gnomad4 AMR exome

AF:

0.000979

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.00928

AC:

1414

AN:

152326

Hom.:

Cov.:

AF XY:

0.00895

AC XY:

667

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00535

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bosley-Salih-Alorainy syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

9.4

DANN

Benign

0.80

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