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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	NM_024012.4	MANE Select	c.741+117G>T		intron	N/A	NP_076917.1	A4D2N2
	HTR5A-AS1	NR_038945.1		n.-200C>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.741+117G>T	intron	N/A	ENSP00000287907.2	P47898
HTR5A-AS1	ENST00000671665.1		n.694C>A	non_coding_transcript_exon	Exon 1 of 2
HTR5A	ENST00000649716.1		n.213+117G>T	intron	N/A	ENSP00000497222.1	A0A3B3ISH0

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over