Genetic Variant HTR5A:p.Ser189Ser (chr7-155071466-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_024012.4(HTR5A):c.567C>T(p.Ser189Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,614,178 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 13 hom. )

Consequence

HTR5A
NM_024012.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.49

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 7-155071466-C-T is Benign according to our data. Variant chr7-155071466-C-T is described in ClinVar as [Benign]. Clinvar id is 708987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.567C>T	p.Ser189Ser	synonymous_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1	P47898A4D2N2
HTR5A-AS1	NR_038945.1 link	n.92G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3 link	c.567C>T	p.Ser189Ser	synonymous_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2		P47898

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00227

AC:

571

AN:

251204

AF XY:

0.00239

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00390

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00243

AC:

3555

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

1826

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.00418

AC:

187

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00442

AC:

381

AN:

86254

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00249

AC:

2766

AN:

1112010

Other (OTH)

AF:

0.00268

AC:

162

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

218

436

653

871

1089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152314

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41572

American (AMR)

AF:

0.00274

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00393

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00207

AC:

141

AN:

68026

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00201

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.6

(source)

DANN

Benign

0.92

PhyloP100

-2.5

Mutation Taster

=298/2

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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7-155071466-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over