dbSNP rs3734119: HTR4:c.508-36T>C (chr5-148510060-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000870.7(HTR4):c.508-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,400,284 control chromosomes in the GnomAD database, including 9,018 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 0.15 ( 3322 hom., cov: 31)

Exomes 𝑓: 0.066 ( 5696 hom. )

Consequence

HTR4
NM_000870.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.610

Publications

2 publications found

Variant links:

Genes affected

HTR4 (HGNC:5299): (5-hydroxytryptamine receptor 4) This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]

HTR4 links:

ENSG00000300418 (HGNC:):

ENSG00000300418 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7 link	c.508-36T>C		intron_variant	Intron 5 of 6	ENST00000377888.8	NP_000861.1	Q13639-1A0A2D3FAF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8 link	c.508-36T>C		intron_variant	Intron 5 of 6	1	NM_000870.7	ENSP00000367120.4		Q13639-1

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23493

AN:

151686

Hom.:

3321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.0769

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.122

AC:

20658

AN:

169514

AF XY:

0.111

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.0466

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.0719

Gnomad NFE exome

AF:

0.0499

Gnomad OTH exome

AF:

0.0903

GnomAD4 exome

AF:

0.0660

AC:

82419

AN:

1248480

Hom.:

5696

Cov.:

AF XY:

0.0646

AC XY:

40072

AN XY:

620762

show subpopulations

African (AFR)

AF:

0.370

AC:

10408

AN:

28110

American (AMR)

AF:

0.195

AC:

6190

AN:

31792

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

873

AN:

21454

East Asian (EAS)

AF:

0.287

AC:

10686

AN:

37278

South Asian (SAS)

AF:

0.0733

AC:

5198

AN:

70932

European-Finnish (FIN)

AF:

0.0706

AC:

3565

AN:

50518

Middle Eastern (MID)

AF:

0.0333

AC:

173

AN:

5196

European-Non Finnish (NFE)

AF:

0.0431

AC:

40927

AN:

950666

Other (OTH)

AF:

0.0837

AC:

4399

AN:

52534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3623

7247

10870

14494

18117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1818

3636

5454

7272

9090

<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:

0.155

AC:

23516

AN:

151804

Hom.:

3322

Cov.:

AF XY:

0.155

AC XY:

11495

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.366

AC:

15118

AN:

41292

American (AMR)

AF:

0.159

AC:

2426

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

130

AN:

3472

East Asian (EAS)

AF:

0.280

AC:

1445

AN:

5158

South Asian (SAS)

AF:

0.0765

AC:

366

AN:

4782

European-Finnish (FIN)

AF:

0.0644

AC:

682

AN:

10588

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0445

AC:

3025

AN:

67946

Other (OTH)

AF:

0.129

AC:

272

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

830

1660

2491

3321

4151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.0956

Hom.:

320

Bravo

AF:

0.171

Asia WGS

AF:

0.162

AC:

561

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

(source)

DANN

Benign

0.64

PhyloP100

0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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