NM_002141.5:c.285C>T

Variant names:

• chr7-27130449-G-A
• rs1785489139
• NM_002141.5:c.285C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_002141.5(HOXA4):​c.285C>T​(p.Ala95Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXA4 NM_002141.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0530
• Publications: 0 publications found

Genes affected

HOXA4 (HGNC:5105): (homeobox A4) 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. [provided by RefSeq, Jul 2008]

HOXA3 (HGNC:5104): (homeobox A3) 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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000273433 (HGNC:):

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

HOXA-AS2 (HGNC:43745): (HOXA cluster antisense RNA 2) This gene produces a long non-coding RNA that promotes cell proliferation. This transcript may interact with enhancer of zeste homolog 2 Polycomb repressive complex to repress gene expression. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-27130449-G-A is Benign according to our data. Variant chr7-27130449-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3032651.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.053 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002141.5. 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
	HOXA4	NM_002141.5	MANE Select	c.285C>T	p.Ala95Ala	synonymous	Exon 1 of 2	NP_002132.3
	HOXA3	NM_153631.3	MANE Select	c.-389-3379C>T		intron	N/A	NP_705895.1	O43365
	HOXA3	NM_001384335.1		c.-505-3379C>T		intron	N/A	NP_001371264.1	O43365

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA4	ENST00000360046.10	TSL:1 MANE Select	c.285C>T	p.Ala95Ala	synonymous	Exon 1 of 2	ENSP00000353151.5	Q00056
	HOXA4	ENST00000610970.1	TSL:1	c.285C>T	p.Ala95Ala	synonymous	Exon 1 of 2	ENSP00000479166.1	Q00056
	HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.-389-3379C>T		intron	N/A	ENSP00000484411.1	O43365

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1068632 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 507286

African (AFR) AF: 0.00 AC: 0 AN: 21100

American (AMR) AF: 0.00 AC: 0 AN: 7696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12474

East Asian (EAS) AF: 0.00 AC: 0 AN: 23080

South Asian (SAS) AF: 0.00 AC: 0 AN: 24558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913104

Other (OTH) AF: 0.00 AC: 0 AN: 41738

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HOXA4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.92
PhyloP100		-0.053
PromoterAI		-0.040	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: rs1785489139; hg19: chr7-27170068;