chr7-27129100-C-T

Variant names:

• chr7-27129100-C-T
• rs4722662
• NM_002141.5:c.*125G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002141.5(HOXA4):​c.*125G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 729,228 control chromosomes in the GnomAD database, including 337,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68802 hom., cov: 33)
  • Exomes 𝑓: 0.96 (268501 hom.)
• Consequence: HOXA4 NM_002141.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08
• Publications: 6 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-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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-27129100-C-T is Benign according to our data. Variant chr7-27129100-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182927.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.*125G>A		3_prime_UTR	Exon 2 of 2	NP_002132.3
	HOXA3	NM_153631.3	MANE Select	c.-389-2030G>A		intron	N/A	NP_705895.1	O43365
	HOXA3	NM_001384335.1		c.-505-2030G>A		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.*125G>A		3_prime_UTR	Exon 2 of 2	ENSP00000353151.5	Q00056
	HOXA4	ENST00000610970.1	TSL:1	c.*125G>A		3_prime_UTR	Exon 2 of 2	ENSP00000479166.1	Q00056
	HOXA4	ENST00000511914.1	TSL:1	c.*125G>A		3_prime_UTR	Exon 2 of 2	ENSP00000448015.1	H0YHX3

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144562 AN: 152190 Hom.: 68744 Cov.: 33

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.965 AC: 556484 AN: 576920 Hom.: 268501 Cov.: 5 AF XY: 0.963 AC XY: 299992 AN XY: 311490

African (AFR) AF: 0.897 AC: 14014 AN: 15622

American (AMR) AF: 0.972 AC: 34214 AN: 35210

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 17422 AN: 17794

East Asian (EAS) AF: 0.998 AC: 35519 AN: 35606

South Asian (SAS) AF: 0.938 AC: 57004 AN: 60804

European-Finnish (FIN) AF: 0.963 AC: 42971 AN: 44640

Middle Eastern (MID) AF: 0.956 AC: 2210 AN: 2312

European-Non Finnish (NFE) AF: 0.968 AC: 323596 AN: 334268

Other (OTH) AF: 0.963 AC: 29534 AN: 30664

GnomAD4 genome AF: 0.950 AC: 144680 AN: 152308 Hom.: 68802 Cov.: 33 AF XY: 0.949 AC XY: 70658 AN XY: 74474

African (AFR) AF: 0.901 AC: 37424 AN: 41524

American (AMR) AF: 0.967 AC: 14806 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3410 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5180 AN: 5188

South Asian (SAS) AF: 0.944 AC: 4558 AN: 4826

European-Finnish (FIN) AF: 0.957 AC: 10171 AN: 10626

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

European-Non Finnish (NFE) AF: 0.970 AC: 65979 AN: 68044

Other (OTH) AF: 0.947 AC: 2001 AN: 2114

Alfa AF: 0.965 Hom.: 36264

Bravo AF: 0.948

Asia WGS AF: 0.968 AC: 3368 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	-0.42
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		1.1
Mutation Taster		=99/1	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: rs4722662; hg19: chr7-27168719;