7-27094259-C-T

Position:

• chr7-27094259-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005522.5(HOXA1):​c.*181G>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 0.00527 in 607,168 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (15 hom.)
• Consequence: HOXA1 NM_005522.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.150

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA1	NM_005522.5	c.*181G>A		3_prime_UTR_variant	2/2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.*572G>A		3_prime_UTR_variant	3/3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460	c.*181G>A		3_prime_UTR_variant	2/2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633	c.*572G>A		3_prime_UTR_variant	3/3	1		ENSP00000347851.5

Frequencies

GnomAD3 genomes AF: 0.00499 AC: 760 AN: 152166 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00551

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00852

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00536 AC: 2439 AN: 454884 Hom.: 15 Cov.: 4 AF XY: 0.00504 AC XY: 1214 AN XY: 240868

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00546

Gnomad4 ASJ exome AF: 0.000646

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000744

Gnomad4 FIN exome AF: 0.00160

Gnomad4 NFE exome AF: 0.00760

Gnomad4 OTH exome AF: 0.00540

GnomAD4 genome AF: 0.00499 AC: 760 AN: 152284 Hom.: 2 Cov.: 33 AF XY: 0.00481 AC XY: 358 AN XY: 74444

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00550

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00853

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00552 Hom.: 0

Bravo AF: 0.00495

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bosley-Salih-Alorainy syndrome Uncertain:1

Uncertain significance, 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	-0.79
CADD	Benign	2.1
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs145102625; hg19: chr7-27133878;