7-27142626-C-T

Variant names:

• chr7-27142626-C-T
• rs3757640
• NM_153631.3:c.-493-2440G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153631.3(HOXA3):​c.-493-2440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 189,504 control chromosomes in the GnomAD database, including 38,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29690 hom., cov: 33)
  • Exomes 𝑓: 0.67 (8901 hom.)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 13 publications found

Genes affected

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]

HOXA5 (HGNC:5106): (homeobox A5) 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. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis. [provided by RefSeq, Jul 2008]

ENSG00000273433 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA3	NM_153631.3	c.-493-2440G>A		intron_variant	Intron 1 of 5	ENST00000612286.5	NP_705895.1
HOXA5	NM_019102.4	c.562+420G>A		intron_variant	Intron 1 of 1	ENST00000222726.4	NP_061975.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA3	ENST00000612286.5	c.-493-2440G>A		intron_variant	Intron 1 of 5	2	NM_153631.3	ENSP00000484411.1
HOXA5	ENST00000222726.4	c.562+420G>A		intron_variant	Intron 1 of 1	1	NM_019102.4	ENSP00000222726.3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92206 AN: 151958 Hom.: 29683 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.675 AC: 25256 AN: 37428 Hom.: 8901 AF XY: 0.682 AC XY: 12687 AN XY: 18604

African (AFR) AF: 0.345 AC: 465 AN: 1346

American (AMR) AF: 0.582 AC: 1152 AN: 1978

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 960 AN: 1312

East Asian (EAS) AF: 0.620 AC: 1219 AN: 1966

South Asian (SAS) AF: 0.728 AC: 719 AN: 988

European-Finnish (FIN) AF: 0.585 AC: 974 AN: 1664

Middle Eastern (MID) AF: 0.739 AC: 136 AN: 184

European-Non Finnish (NFE) AF: 0.707 AC: 18080 AN: 25568

Other (OTH) AF: 0.640 AC: 1551 AN: 2422

GnomAD4 genome AF: 0.607 AC: 92241 AN: 152076 Hom.: 29690 Cov.: 33 AF XY: 0.604 AC XY: 44897 AN XY: 74324

African (AFR) AF: 0.382 AC: 15852 AN: 41454

American (AMR) AF: 0.627 AC: 9580 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2642 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3161 AN: 5164

South Asian (SAS) AF: 0.740 AC: 3567 AN: 4822

European-Finnish (FIN) AF: 0.599 AC: 6343 AN: 10586

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.719 AC: 48917 AN: 67990

Other (OTH) AF: 0.652 AC: 1375 AN: 2110

Alfa AF: 0.700 Hom.: 50131

Bravo AF: 0.595

Asia WGS AF: 0.645 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		-0.23
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: rs3757640; hg19: chr7-27182245;