7-27094259-C-T

Variant names:

• chr7-27094259-C-T
• rs145102625
• NM_005522.5:c.*181G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• human HOXA1 syndromes

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bosley-Salih-Alorainy syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005522.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA1	NM_005522.5	MANE Select	c.*181G>A		3_prime_UTR	Exon 2 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.*572G>A		3_prime_UTR	Exon 3 of 3	NP_705873.3	P49639-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA1	ENST00000643460.2	MANE Select	c.*181G>A		3_prime_UTR	Exon 2 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.*572G>A		3_prime_UTR	Exon 3 of 3	ENSP00000347851.5	E7ERT8

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

African (AFR) AF: 0.00158 AC: 20 AN: 12640

American (AMR) AF: 0.00546 AC: 111 AN: 20332

Ashkenazi Jewish (ASJ) AF: 0.000646 AC: 9 AN: 13940

East Asian (EAS) AF: 0.00 AC: 0 AN: 30456

South Asian (SAS) AF: 0.000744 AC: 35 AN: 47020

European-Finnish (FIN) AF: 0.00160 AC: 47 AN: 29286

Middle Eastern (MID) AF: 0.000504 AC: 1 AN: 1984

European-Non Finnish (NFE) AF: 0.00760 AC: 2075 AN: 273106

Other (OTH) AF: 0.00540 AC: 141 AN: 26120

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

African (AFR) AF: 0.00159 AC: 66 AN: 41570

American (AMR) AF: 0.00550 AC: 84 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00853 AC: 580 AN: 68034

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00552 Hom.: 0

Bravo AF: 0.00495

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Bosley-Salih-Alorainy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs145102625; hg19: chr7-27133878;