Genetic Variant HOTTIP:n.408C>G (chr7-27200863-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000421733.1(HOTTIP):n.408C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,586 control chromosomes in the GnomAD database, including 10,959 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 0.35 ( 10907 hom., cov: 32)

Exomes 𝑓: 0.41 ( 52 hom. )

Consequence

HOTTIP
ENST00000421733.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0450

Publications

22 publications found

Variant links:

Genes affected

HOTTIP (HGNC:37461): (HOXA distal transcript antisense RNA) This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation. [provided by RefSeq, Dec 2017]

HOTTIP links:

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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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOTTIP	NR_037843.3 link	n.342C>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
HOTTIP	ENST00000421733.1 link	n.408C>G	non_coding_transcript_exon_variant	Exon 2 of 2	5
HOTTIP	ENST00000472494.2 link	n.337C>G	non_coding_transcript_exon_variant	Exon 2 of 2	2
HOTTIP	ENST00000605136.7 link	n.333C>G	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53315

AN:

151970

Hom.:

10904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.397

GnomAD4 exome

AF:

0.412

AC:

206

AN:

500

Hom.:

Cov.:

AF XY:

0.410

AC XY:

110

AN XY:

268

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.416

AC:

139

AN:

334

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.390

AC:

AN:

136

Other (OTH)

AF:

0.409

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.351

AC:

53323

AN:

152086

Hom.:

10907

Cov.:

AF XY:

0.349

AC XY:

25944

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.131

AC:

5438

AN:

41524

American (AMR)

AF:

0.336

AC:

5127

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1600

AN:

3466

East Asian (EAS)

AF:

0.491

AC:

2532

AN:

5160

South Asian (SAS)

AF:

0.418

AC:

2013

AN:

4820

European-Finnish (FIN)

AF:

0.388

AC:

4096

AN:

10570

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31155

AN:

67956

Other (OTH)

AF:

0.402

AC:

848

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1646

3293

4939

6586

8232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.392

Hom.:

1589

Bravo

AF:

0.336

Asia WGS

AF:

0.440

AC:

1532

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.1

(source)

DANN

Benign

0.60

PhyloP100

0.045

Splicing

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