chr7-27095691-GTGGCGA-G

Variant names:

• chr7-27095691-GTGGCGA-G
• rs767586523
• NM_005522.5:c.216_221delTCGCCA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_005522.5(HOXA1):​c.216_221delTCGCCA​(p.Arg73_His74del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,544,470 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. H72H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00044 (4 hom.)
• Consequence: HOXA1 NM_005522.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.13
• 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.

• BP3: Nonframeshift variant in repetitive region in NM_005522.5
• BP6: Variant 7-27095691-GTGGCGA-G is Benign according to our data. Variant chr7-27095691-GTGGCGA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3051297.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	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.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.216_221delTCGCCA	p.Arg73_His74del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000347851.5	E7ERT8
	HOTAIRM1	ENST00000495032.1	TSL:5	n.26+23_26+28delCGATGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000442 AC: 66 AN: 149486 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000404

Gnomad OTH AF: 0.000488

GnomAD2 exomes AF: 0.000507 AC: 126 AN: 248578 AF XY: 0.000684

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000332

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000440 AC: 614 AN: 1394864 Hom.: 4 AF XY: 0.000503 AC XY: 350 AN XY: 695830

African (AFR) AF: 0.000513 AC: 17 AN: 33118

American (AMR) AF: 0.000181 AC: 8 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.000117 AC: 3 AN: 25538

East Asian (EAS) AF: 0.000158 AC: 6 AN: 38032

South Asian (SAS) AF: 0.00245 AC: 206 AN: 84014

European-Finnish (FIN) AF: 0.0000769 AC: 4 AN: 52042

Middle Eastern (MID) AF: 0.000537 AC: 3 AN: 5582

European-Non Finnish (NFE) AF: 0.000320 AC: 337 AN: 1054202

Other (OTH) AF: 0.000516 AC: 30 AN: 58174

GnomAD4 genome AF: 0.000441 AC: 66 AN: 149606 Hom.: 0 Cov.: 28 AF XY: 0.000480 AC XY: 35 AN XY: 72968

African (AFR) AF: 0.000582 AC: 24 AN: 41258

American (AMR) AF: 0.000199 AC: 3 AN: 15062

Ashkenazi Jewish (ASJ) AF: 0.000295 AC: 1 AN: 3394

East Asian (EAS) AF: 0.000209 AC: 1 AN: 4788

South Asian (SAS) AF: 0.00193 AC: 9 AN: 4668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10354

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

European-Non Finnish (NFE) AF: 0.000404 AC: 27 AN: 66818

Other (OTH) AF: 0.000483 AC: 1 AN: 2072

Alfa AF: 0.000434 Hom.: 0

EpiCase AF: 0.000218

EpiControl AF: 0.000475

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HOXA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=194/6	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767586523; hg19: chr7-27135310; COSMIC: COSV107296641; COSMIC: COSV107296641;