dbSNP rs78899540: HOXA5:c.*362T>G (chr7-27141473-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019102.4(HOXA5):c.*362T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0383 in 206,864 control chromosomes in the GnomAD database, including 210 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 0.039 ( 154 hom., cov: 33)

Exomes 𝑓: 0.038 ( 56 hom. )

Consequence

HOXA5
NM_019102.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.31

Publications

9 publications found

Variant links:

Genes affected

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]

HOXA5 links:

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]

HOXA3 links:

ENSG00000273433 (HGNC:):

ENSG00000273433 links:

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

HOXA-AS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA5	NM_019102.4 link	c.*362T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000222726.4	NP_061975.2	P20719
HOXA3	NM_153631.3 link	c.-493-1287T>G		intron_variant	Intron 1 of 5	ENST00000612286.5	NP_705895.1	O43365A4D182A0A024RA33B3KPN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA5	ENST00000222726.4 link	c.*362T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_019102.4	ENSP00000222726.3		P20719
HOXA3	ENST00000612286.5 link	c.-493-1287T>G		intron_variant	Intron 1 of 5	2	NM_153631.3	ENSP00000484411.1		O43365

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

5869

AN:

152192

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0585

Gnomad OTH

AF:

0.0449

GnomAD4 exome

AF:

0.0377

AC:

2055

AN:

54554

Hom.:

Cov.:

AF XY:

0.0372

AC XY:

1065

AN XY:

28600

show subpopulations

African (AFR)

AF:

0.0157

AC:

AN:

1080

American (AMR)

AF:

0.0375

AC:

135

AN:

3602

Ashkenazi Jewish (ASJ)

AF:

0.0360

AC:

AN:

1360

East Asian (EAS)

AF:

0.00

AC:

AN:

2520

South Asian (SAS)

AF:

0.0204

AC:

138

AN:

6756

European-Finnish (FIN)

AF:

0.0165

AC:

AN:

2362

Middle Eastern (MID)

AF:

0.0446

AC:

AN:

202

European-Non Finnish (NFE)

AF:

0.0461

AC:

1557

AN:

33776

Other (OTH)

AF:

0.0383

AC:

111

AN:

2896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

105

209

314

418

523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0385

AC:

5866

AN:

152310

Hom.:

154

Cov.:

AF XY:

0.0360

AC XY:

2681

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0168

AC:

699

AN:

41582

American (AMR)

AF:

0.0380

AC:

582

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

149

AN:

3472

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.0265

AC:

128

AN:

4830

European-Finnish (FIN)

AF:

0.0191

AC:

202

AN:

10600

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0584

AC:

3974

AN:

68014

Other (OTH)

AF:

0.0440

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

301

601

902

1202

1503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0417

Hom.:

Bravo

AF:

0.0401

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

6.3

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over