7-27095700-G-A

Variant names:

• chr7-27095700-G-A
• rs2074398
• NM_005522.5:c.213C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005522.5(HOXA1):​c.213C>T​(p.His71His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,092,248 control chromosomes in the GnomAD database, including 810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (61 hom., cov: 30)
  • Exomes 𝑓: 0.049 (749 hom.)
• Consequence: HOXA1 NM_005522.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.195
• Publications: 3 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-27095700-G-A is Benign according to our data. Variant chr7-27095700-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 359966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.195 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

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.213C>T	p.His71His	synonymous	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.213C>T	p.His71His	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.213C>T	p.His71His	synonymous	Exon 1 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.213C>T	p.His71His	synonymous	Exon 1 of 3	ENSP00000347851.5	E7ERT8
	HOTAIRM1	ENST00000495032.1	TSL:5	n.26+28G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3606 AN: 150004 Hom.: 61 Cov.: 30

Gnomad AFR AF: 0.00660

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0442

Gnomad EAS AF: 0.000784

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0333

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0317

GnomAD2 exomes AF: 0.0302 AC: 6222 AN: 206014 AF XY: 0.0312

Gnomad AFR exome AF: 0.00646

Gnomad AMR exome AF: 0.0257

Gnomad ASJ exome AF: 0.0584

Gnomad EAS exome AF: 0.00107

Gnomad FIN exome AF: 0.0293

Gnomad NFE exome AF: 0.0395

Gnomad OTH exome AF: 0.0345

GnomAD4 exome AF: 0.0493 AC: 46489 AN: 942132 Hom.: 749 Cov.: 41 AF XY: 0.0504 AC XY: 23000 AN XY: 456538

African (AFR) AF: 0.00747 AC: 186 AN: 24896

American (AMR) AF: 0.0461 AC: 982 AN: 21304

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 1134 AN: 15066

East Asian (EAS) AF: 0.00138 AC: 28 AN: 20258

South Asian (SAS) AF: 0.0471 AC: 1625 AN: 34508

European-Finnish (FIN) AF: 0.0513 AC: 1378 AN: 26878

Middle Eastern (MID) AF: 0.0592 AC: 233 AN: 3938

European-Non Finnish (NFE) AF: 0.0516 AC: 39082 AN: 757878

Other (OTH) AF: 0.0492 AC: 1841 AN: 37406

GnomAD4 genome AF: 0.0240 AC: 3606 AN: 150116 Hom.: 61 Cov.: 30 AF XY: 0.0237 AC XY: 1739 AN XY: 73272

African (AFR) AF: 0.00658 AC: 270 AN: 41022

American (AMR) AF: 0.0306 AC: 460 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.0442 AC: 148 AN: 3350

East Asian (EAS) AF: 0.000786 AC: 4 AN: 5092

South Asian (SAS) AF: 0.0194 AC: 90 AN: 4638

European-Finnish (FIN) AF: 0.0243 AC: 254 AN: 10452

Middle Eastern (MID) AF: 0.0360 AC: 10 AN: 278

European-Non Finnish (NFE) AF: 0.0343 AC: 2305 AN: 67266

Other (OTH) AF: 0.0314 AC: 65 AN: 2072

Alfa AF: 0.0198 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bilateral microtia-deafness-cleft palate syndrome (1)
-	-	1	Bosley-Salih-Alorainy syndrome (1)
-	-	1	HOXA1-related disorder (1)
-	-	1	Human HOXA1 syndromes (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.6
DANN	Benign	0.94
PhyloP100		0.20
PromoterAI		0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2074398; hg19: chr7-27135319; COSMIC: COSV56065447; COSMIC: COSV56065447;