rs886062260

Variant names:

• chr7-27095697-A-G
• rs886062260
• NM_005522.5:c.216T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_005522.5(HOXA1):​c.216T>C​(p.His72His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 949,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000042 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: HOXA1 NM_005522.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: -0.358
• 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]

HOTAIRM1 (HGNC:37117): (HOXA transcript antisense RNA, myeloid-specific 1) This non-coding locus is located in the HOX gene cluster. Transcription of this locus is induced by retinoic acid, and transcripts likely function in regulation of myelopoiesis through transcriptional activation of several genes in the HOXA cluster, in addition to several beta-2 integrins. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 7-27095697-A-G is Benign according to our data. Variant chr7-27095697-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 359965.
• BP7: Synonymous conserved (PhyloP=-0.358 with no splicing effect.

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.216T>C	p.His72His	synonymous	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.216T>C	p.His72His	synonymous	Exon 1 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.216T>C	p.His72His	synonymous	Exon 1 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.216T>C	p.His72His	synonymous	Exon 1 of 3	ENSP00000347851.5	E7ERT8
	HOTAIRM1	ENST00000495032.1	TSL:5	n.26+25A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000424 AC: 6 AN: 141484 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000799

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000140 AC: 113 AN: 808070 Hom.: 0 Cov.: 38 AF XY: 0.000162 AC XY: 63 AN XY: 388578

African (AFR) AF: 0.00 AC: 0 AN: 25106

American (AMR) AF: 0.0000609 AC: 1 AN: 16414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12048

East Asian (EAS) AF: 0.000526 AC: 9 AN: 17096

South Asian (SAS) AF: 0.000510 AC: 13 AN: 25506

European-Finnish (FIN) AF: 0.0000489 AC: 1 AN: 20436

Middle Eastern (MID) AF: 0.000294 AC: 1 AN: 3402

European-Non Finnish (NFE) AF: 0.000128 AC: 84 AN: 655824

Other (OTH) AF: 0.000124 AC: 4 AN: 32238

GnomAD4 genome AF: 0.0000424 AC: 6 AN: 141484 Hom.: 0 Cov.: 30 AF XY: 0.0000290 AC XY: 2 AN XY: 69068

African (AFR) AF: 0.0000249 AC: 1 AN: 40118

American (AMR) AF: 0.00 AC: 0 AN: 14062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3162

East Asian (EAS) AF: 0.00 AC: 0 AN: 4664

South Asian (SAS) AF: 0.00 AC: 0 AN: 4256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000799 AC: 5 AN: 62564

Other (OTH) AF: 0.00 AC: 0 AN: 1928

Alfa AF: 0.000107 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Bosley-Salih-Alorainy syndrome (1)
-	1	-	Human HOXA1 syndromes (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		-0.36
PromoterAI		-0.069	Neutral

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: rs886062260; hg19: chr7-27135316;