Genetic Variant HTR5A:p.His100His (chr7-155071199-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_024012.4(HTR5A):c.300C>T(p.His100His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,602,758 control chromosomes in the GnomAD database, including 221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 130 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 91 hom. )

Consequence

HTR5A
NM_024012.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.07

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 7-155071199-C-T is Benign according to our data. Variant chr7-155071199-C-T is described in ClinVar as [Benign]. Clinvar id is 783512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.300C>T	p.His100His	synonymous_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1	P47898A4D2N2
HTR5A-AS1	NR_038945.1 link	n.359G>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.300C>T	p.His100His	synonymous_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2		P47898

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3222

AN:

152208

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00955

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.00571

AC:

1371

AN:

240306

AF XY:

0.00398

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000351

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00223

AC:

3240

AN:

1450432

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1379

AN XY:

722032

show subpopulations

African (AFR)

AF:

0.0768

AC:

2572

AN:

33472

American (AMR)

AF:

0.00403

AC:

180

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42332

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000170

AC:

189

AN:

1111820

Other (OTH)

AF:

0.00458

AC:

276

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

231

462

692

923

1154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0212

AC:

3230

AN:

152326

Hom.:

130

Cov.:

AF XY:

0.0199

AC XY:

1485

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0730

AC:

3033

AN:

41564

American (AMR)

AF:

0.00954

AC:

146

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68034

Other (OTH)

AF:

0.0118

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00977

Hom.:

Bravo

AF:

0.0237

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

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

-0.41

CADD

Benign

3.4

(source)

DANN

Benign

0.94

PhyloP100

-1.1

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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7-155071199-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