dbSNP rs1421125: HRH4:c.*385G>T (chr18-24477947-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021624.4(HRH4):c.*385G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 161,962 control chromosomes in the GnomAD database, including 8,716 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 0.31 ( 8090 hom., cov: 34)

Exomes 𝑓: 0.34 ( 626 hom. )

Consequence

HRH4
NM_021624.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.867

Publications

10 publications found

Variant links:

Genes affected

HRH4 (HGNC:17383): (histamine receptor H4) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by a family of histamine receptors, which are a subset of the G-protein coupled receptor superfamily. This gene encodes a histamine receptor that is predominantly expressed in haematopoietic cells. The protein is thought to play a role in inflammation and allergy reponses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

HRH4 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HRH4	NM_021624.4 link	c.*385G>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000256906.5	NP_067637.2	Q9H3N8-1
HRH4	NM_001143828.2 link	c.*385G>T	3_prime_UTR_variant	Exon 2 of 2		NP_001137300.1	Q9H3N8-2
HRH4	NM_001160166.2 link	c.*1190G>T	3_prime_UTR_variant	Exon 2 of 2		NP_001153638.1	Q9H3N8B2KJ49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH4	ENST00000256906.5 link	c.*385G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_021624.4	ENSP00000256906.4		Q9H3N8-1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47667

AN:

152096

Hom.:

8092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.344

AC:

3352

AN:

9746

Hom.:

626

Cov.:

AF XY:

0.348

AC XY:

1823

AN XY:

5240

show subpopulations

African (AFR)

AF:

0.256

AC:

AN:

156

American (AMR)

AF:

0.245

AC:

345

AN:

1410

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

AN:

196

East Asian (EAS)

AF:

0.0788

AC:

AN:

406

South Asian (SAS)

AF:

0.320

AC:

307

AN:

958

European-Finnish (FIN)

AF:

0.264

AC:

AN:

182

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.387

AC:

2315

AN:

5988

Other (OTH)

AF:

0.383

AC:

163

AN:

426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

109

218

326

435

544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.313

AC:

47665

AN:

152216

Hom.:

8090

Cov.:

AF XY:

0.309

AC XY:

23015

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.211

AC:

8750

AN:

41534

American (AMR)

AF:

0.265

AC:

4050

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

1433

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

567

AN:

5178

South Asian (SAS)

AF:

0.361

AC:

1744

AN:

4828

European-Finnish (FIN)

AF:

0.315

AC:

3336

AN:

10588

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26506

AN:

68006

Other (OTH)

AF:

0.337

AC:

712

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1704

3408

5111

6815

8519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.367

Hom.:

39170

Bravo

AF:

0.302

Asia WGS

AF:

0.225

AC:

783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

(source)

DANN

Benign

0.61

PhyloP100

0.87

Mutation Taster

=100/0

polymorphism (auto)

(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