rs7786554

Variant names:

• chr7-27093350-G-A
• rs7786554
• NM_005522.5:c.*1090C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005522.5(HOXA1):​c.*1090C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00584 in 152,204 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXA1 NM_005522.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.43

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 -10 ACMG points.

• BP6: Variant 7-27093350-G-A is Benign according to our data. Variant chr7-27093350-G-A is described in ClinVar as [Benign]. Clinvar id is 908469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00584 (889/152204) while in subpopulation AFR AF= 0.0175 (726/41506). AF 95% confidence interval is 0.0164. There are 10 homozygotes in gnomad4. There are 414 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA1	NM_005522.5	c.*1090C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.*1481C>T		3_prime_UTR_variant	Exon 3 of 3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460	c.*1090C>T		3_prime_UTR_variant	Exon 2 of 2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633	c.*1481C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000347851.5

Frequencies

GnomAD3 genomes AF: 0.00585 AC: 889 AN: 152086 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.00478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 438 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 264

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00584 AC: 889 AN: 152204 Hom.: 10 Cov.: 33 AF XY: 0.00556 AC XY: 414 AN XY: 74412

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00296 Hom.: 4

Bravo AF: 0.00617

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Human HOXA1 syndromes Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Benign	0.92

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: rs7786554; hg19: chr7-27132969;