NM_005522.5:c.210C>T

Variant names:

• chr7-27095703-G-A
• rs199620262
• NM_005522.5:c.210C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_005522.5(HOXA1):​c.210C>T​(p.His70His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,567,694 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: HOXA1 NM_005522.5 synonymous
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.78
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.
• 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.210C>T	p.His70His	synonymous	Exon 1 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.210C>T	p.His70His	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.210C>T	p.His70His	synonymous	Exon 1 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.210C>T	p.His70His	synonymous	Exon 1 of 3	ENSP00000347851.5	E7ERT8
	HOTAIRM1	ENST00000495032.1	TSL:5	n.26+31G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000462 AC: 70 AN: 151394 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.00170

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.000628 AC: 156 AN: 248326 AF XY: 0.000781

Gnomad AFR exome AF: 0.000619

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00185

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000332

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000544 AC: 771 AN: 1416180 Hom.: 4 Cov.: 38 AF XY: 0.000588 AC XY: 413 AN XY: 702634

African (AFR) AF: 0.000514 AC: 17 AN: 33080

American (AMR) AF: 0.000235 AC: 10 AN: 42636

Ashkenazi Jewish (ASJ) AF: 0.000122 AC: 3 AN: 24494

East Asian (EAS) AF: 0.00388 AC: 150 AN: 38672

South Asian (SAS) AF: 0.00259 AC: 205 AN: 79222

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51234

Middle Eastern (MID) AF: 0.000546 AC: 3 AN: 5490

European-Non Finnish (NFE) AF: 0.000322 AC: 349 AN: 1083136

Other (OTH) AF: 0.000567 AC: 33 AN: 58216

GnomAD4 genome AF: 0.000462 AC: 70 AN: 151514 Hom.: 0 Cov.: 30 AF XY: 0.000513 AC XY: 38 AN XY: 74002

African (AFR) AF: 0.000531 AC: 22 AN: 41408

American (AMR) AF: 0.000198 AC: 3 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3366

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5142

South Asian (SAS) AF: 0.00170 AC: 8 AN: 4698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000369 AC: 25 AN: 67838

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000240 Hom.: 0

EpiCase AF: 0.000273

EpiControl AF: 0.000475

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Human HOXA1 syndromes (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.0
DANN	Benign	0.94
PhyloP100		1.8
PromoterAI		0.029	Neutral
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: rs199620262; hg19: chr7-27135322;