chr7-27093877-C-G

Position:

• chr7-27093877-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005522.5(HOXA1):​c.*563G>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 0.00492 in 155,084 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: HOXA1 NM_005522.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• 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.*563G>C		3_prime_UTR_variant	2/2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.*954G>C		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.*563G>C		3_prime_UTR_variant	2/2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633	c.*954G>C		3_prime_UTR_variant	3/3	1		ENSP00000347851.5

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 152144 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00354 AC: 10 AN: 2822 Hom.: 0 Cov.: 0 AF XY: 0.00272 AC XY: 4 AN XY: 1470

Gnomad4 AMR exome AF: 0.00188

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00587

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00495 AC: 753 AN: 152262 Hom.: 2 Cov.: 33 AF XY: 0.00474 AC XY: 353 AN XY: 74454

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00850

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00551 Hom.: 0

Bravo AF: 0.00493

Asia WGS AF: 0.000578 AC: 2 AN: 3476

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	-0.28
CADD	Benign	12
DANN	Benign	0.86

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: rs117011404; hg19: chr7-27133496;