dbSNP rs6320: HTR5A:p.Pro4Pro (chr7-155070911-T-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_024012.4(HTR5A):c.12T>A(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,600,956 control chromosomes in the GnomAD database, including 65,314 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 0.26 ( 5281 hom., cov: 32)

Exomes 𝑓: 0.28 ( 60033 hom. )

Consequence

HTR5A
NM_024012.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.736

Publications

22 publications found

Variant links:

Genes affected

HTR5A (HGNC:5300): (5-hydroxytryptamine receptor 5A) The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

HTR5A links:

HTR5A-AS1 (HGNC:48956): (HTR5A antisense RNA 1)

HTR5A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=-0.736 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.12T>A	p.Pro4Pro	synonymous_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1	P47898A4D2N2
HTR5A-AS1	NR_038945.1 link	n.524+123A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3 link	c.12T>A	p.Pro4Pro	synonymous_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2		P47898

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39345

AN:

151972

Hom.:

5281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.269

GnomAD2 exomes

AF:

0.262

AC:

63551

AN:

242472

AF XY:

0.262

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.285

AC:

412353

AN:

1448866

Hom.:

60033

Cov.:

AF XY:

0.283

AC XY:

204262

AN XY:

720934

show subpopulations

African (AFR)

AF:

0.216

AC:

7212

AN:

33444

American (AMR)

AF:

0.207

AC:

9234

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

5689

AN:

26026

East Asian (EAS)

AF:

0.390

AC:

15460

AN:

39654

South Asian (SAS)

AF:

0.233

AC:

20077

AN:

86082

European-Finnish (FIN)

AF:

0.263

AC:

11198

AN:

42534

Middle Eastern (MID)

AF:

0.258

AC:

1489

AN:

5766

European-Non Finnish (NFE)

AF:

0.293

AC:

325239

AN:

1110460

Other (OTH)

AF:

0.278

AC:

16755

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

17159

34318

51476

68635

85794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10882

21764

32646

43528

54410

<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:

0.259

AC:

39366

AN:

152090

Hom.:

5281

Cov.:

AF XY:

0.257

AC XY:

19137

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.215

AC:

8909

AN:

41478

American (AMR)

AF:

0.225

AC:

3435

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3470

East Asian (EAS)

AF:

0.368

AC:

1894

AN:

5152

South Asian (SAS)

AF:

0.236

AC:

1135

AN:

4814

European-Finnish (FIN)

AF:

0.266

AC:

2814

AN:

10596

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19422

AN:

67978

Other (OTH)

AF:

0.267

AC:

563

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1511

3022

4532

6043

7554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.198

Hom.:

640

Bravo

AF:

0.257

Asia WGS

AF:

0.286

AC:

993

AN:

3478

EpiCase

AF:

0.275

EpiControl

AF:

0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.7

(source)

DANN

Benign

0.84

PhyloP100

-0.74

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