Genetic Variant HTR5A:c.741+117G>T (chr7-155071757-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_024012.4(HTR5A):c.741+117G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,074,426 control chromosomes in the GnomAD database, including 45,598 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 0.23 ( 4915 hom., cov: 32)

Exomes 𝑓: 0.29 ( 40683 hom. )

Consequence

HTR5A
NM_024012.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

Publications

7 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:

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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=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.741+117G>T		intron_variant	Intron 1 of 1	ENST00000287907.3	NP_076917.1	P47898A4D2N2
HTR5A-AS1	NR_038945.1 link	n.-200C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3 link	c.741+117G>T		intron_variant	Intron 1 of 1	1	NM_024012.4	ENSP00000287907.2		P47898

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34575

AN:

150922

Hom.:

4906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0574

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.277

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.288

AC:

266057

AN:

923396

Hom.:

40683

AF XY:

0.290

AC XY:

135113

AN XY:

465900

show subpopulations

African (AFR)

AF:

0.0464

AC:

995

AN:

21456

American (AMR)

AF:

0.198

AC:

5364

AN:

27048

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

4471

AN:

17222

East Asian (EAS)

AF:

0.173

AC:

6168

AN:

35696

South Asian (SAS)

AF:

0.309

AC:

18491

AN:

59810

European-Finnish (FIN)

AF:

0.382

AC:

12669

AN:

33204

Middle Eastern (MID)

AF:

0.264

AC:

791

AN:

2998

European-Non Finnish (NFE)

AF:

0.300

AC:

205102

AN:

683966

Other (OTH)

AF:

0.286

AC:

12006

AN:

41996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9844

19688

29532

39376

49220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5636

11272

16908

22544

28180

<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:

0.229

AC:

34589

AN:

151030

Hom.:

4915

Cov.:

AF XY:

0.232

AC XY:

17134

AN XY:

73864

show subpopulations

African (AFR)

AF:

0.0573

AC:

2319

AN:

40474

American (AMR)

AF:

0.218

AC:

3327

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

889

AN:

3470

East Asian (EAS)

AF:

0.216

AC:

1116

AN:

5166

South Asian (SAS)

AF:

0.307

AC:

1475

AN:

4810

European-Finnish (FIN)

AF:

0.372

AC:

3929

AN:

10562

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.303

AC:

20619

AN:

67974

Other (OTH)

AF:

0.248

AC:

522

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1283

2566

3850

5133

6416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.274

Hom.:

10255

Bravo

AF:

0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.13

(source)

DANN

Benign

0.25

PhyloP100

-0.66

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