Genetic Variant NM_005522.5:c.*56C>A (chr7-27094384-G-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_005522.5(HOXA1):c.*56C>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 0.0949 in 1,186,620 control chromosomes in the GnomAD database, including 6,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 547 hom., cov: 32)

Exomes 𝑓: 0.098 ( 5683 hom. )

Consequence

HOXA1
NM_005522.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.904

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 7-27094384-G-T is Benign according to our data. Variant chr7-27094384-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 359953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA1	NM_005522.5 link	c.*56C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000643460.2	NP_005513.2	P49639
HOXA1	NM_153620.3 link	c.*447C>A		3_prime_UTR_variant	Exon 3 of 3		NP_705873.3	P49639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460 link	c.*56C>A		3_prime_UTR_variant	Exon 2 of 2		NM_005522.5	ENSP00000494260.2		A0A2R8Y4R9
HOXA1	ENST00000355633 link	c.*447C>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000347851.5		E7ERT8

Frequencies

GnomAD3 genomes

AF:

0.0714

AC:

10873

AN:

152186

Hom.:

547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0743

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0733

GnomAD4 exome

AF:

0.0983

AC:

101701

AN:

1034316

Hom.:

5683

Cov.:

AF XY:

0.0971

AC XY:

51782

AN XY:

533358

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.0400

Gnomad4 ASJ exome

AF:

0.0489

Gnomad4 EAS exome

AF:

0.000264

Gnomad4 SAS exome

AF:

0.0573

Gnomad4 FIN exome

AF:

0.0826

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.0837

GnomAD4 genome

AF:

0.0714

AC:

10870

AN:

152304

Hom.:

547

Cov.:

AF XY:

0.0682

AC XY:

5080

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0202

Gnomad4 AMR

AF:

0.0555

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.0743

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.0725

Alfa

AF:

0.0795

Hom.:

Bravo

AF:

0.0664

Asia WGS

AF:

0.0290

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bosley-Salih-Alorainy syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.87

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