7-27128893-C-G

Variant names:

• chr7-27128893-C-G
• rs4722661
• NM_002141.5:c.*332G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002141.5(HOXA4):​c.*332G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 350,990 control chromosomes in the GnomAD database, including 161,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68949 hom., cov: 32)
  • Exomes 𝑓: 0.96 (92394 hom.)
• Consequence: HOXA4 NM_002141.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 3 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]

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]

ENSG00000273433 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-27128893-C-G is Benign according to our data. Variant chr7-27128893-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

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.*332G>C		3_prime_UTR	Exon 2 of 2	NP_002132.3
	HOXA3	NM_153631.3	MANE Select	c.-389-1823G>C		intron	N/A	NP_705895.1	O43365
	HOXA3	NM_001384335.1		c.-505-1823G>C		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.*332G>C		3_prime_UTR	Exon 2 of 2	ENSP00000353151.5	Q00056
	HOXA4	ENST00000610970.1	TSL:1	c.*332G>C		3_prime_UTR	Exon 2 of 2	ENSP00000479166.1	Q00056
	HOXA4	ENST00000511914.1	TSL:1	c.*332G>C		3_prime_UTR	Exon 2 of 2	ENSP00000448015.1	H0YHX3

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144705 AN: 152176 Hom.: 68888 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.964 AC: 191577 AN: 198696 Hom.: 92394 Cov.: 0 AF XY: 0.962 AC XY: 100111 AN XY: 104030

African (AFR) AF: 0.899 AC: 6154 AN: 6846

American (AMR) AF: 0.964 AC: 8047 AN: 8344

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 5714 AN: 5836

East Asian (EAS) AF: 0.997 AC: 11605 AN: 11636

South Asian (SAS) AF: 0.938 AC: 22794 AN: 24292

European-Finnish (FIN) AF: 0.965 AC: 9788 AN: 10138

Middle Eastern (MID) AF: 0.959 AC: 800 AN: 834

European-Non Finnish (NFE) AF: 0.969 AC: 115972 AN: 119682

Other (OTH) AF: 0.965 AC: 10703 AN: 11088

GnomAD4 genome AF: 0.951 AC: 144826 AN: 152294 Hom.: 68949 Cov.: 32 AF XY: 0.950 AC XY: 70742 AN XY: 74470

African (AFR) AF: 0.903 AC: 37532 AN: 41548

American (AMR) AF: 0.969 AC: 14827 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3409 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5165 AN: 5172

South Asian (SAS) AF: 0.945 AC: 4566 AN: 4830

European-Finnish (FIN) AF: 0.959 AC: 10183 AN: 10618

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 65988 AN: 68034

Other (OTH) AF: 0.947 AC: 2003 AN: 2114

Alfa AF: 0.967 Hom.: 3300

Bravo AF: 0.950

Asia WGS AF: 0.971 AC: 3377 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.63
PhyloP100		1.3
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: rs4722661; hg19: chr7-27168512;