Genetic Variant HTR5A:c.-102A>G (chr7-155070798-A-G) – 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.-102A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,236,192 control chromosomes in the GnomAD database, including 51,204 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 ( 4960 hom., cov: 33)

Exomes 𝑓: 0.29 ( 46244 hom. )

Consequence

HTR5A
NM_024012.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.545

Publications

6 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=-0.63).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	NM_024012.4	MANE Select	c.-102A>G		5_prime_UTR	Exon 1 of 2	NP_076917.1
	HTR5A-AS1	NR_038945.1		n.524+236T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.-102A>G	5_prime_UTR	Exon 1 of 2	ENSP00000287907.2
HTR5A-AS1	ENST00000395731.5	TSL:1	n.524+236T>C	intron	N/A
HTR5A-AS1	ENST00000493904.3	TSL:4	n.551+236T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34997

AN:

152046

Hom.:

4950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0662

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.285

AC:

309343

AN:

1084028

Hom.:

46244

Cov.:

AF XY:

0.288

AC XY:

155924

AN XY:

541340

show subpopulations

African (AFR)

AF:

0.0578

AC:

1453

AN:

25148

American (AMR)

AF:

0.200

AC:

5885

AN:

29466

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

4724

AN:

18244

East Asian (EAS)

AF:

0.170

AC:

6339

AN:

37386

South Asian (SAS)

AF:

0.335

AC:

21646

AN:

64634

European-Finnish (FIN)

AF:

0.376

AC:

13315

AN:

35386

Middle Eastern (MID)

AF:

0.266

AC:

1274

AN:

4786

European-Non Finnish (NFE)

AF:

0.294

AC:

241243

AN:

821720

Other (OTH)

AF:

0.285

AC:

13464

AN:

47258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

10988

21975

32963

43950

54938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7306

14612

21918

29224

36530

<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:

0.230

AC:

35017

AN:

152164

Hom.:

4960

Cov.:

AF XY:

0.234

AC XY:

17416

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0661

AC:

2747

AN:

41566

American (AMR)

AF:

0.223

AC:

3406

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

884

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1132

AN:

5156

South Asian (SAS)

AF:

0.337

AC:

1625

AN:

4816

European-Finnish (FIN)

AF:

0.370

AC:

3917

AN:

10580

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.300

AC:

20401

AN:

67970

Other (OTH)

AF:

0.244

AC:

514

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1321

2643

3964

5286

6607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.237

Hom.:

805

Bravo

AF:

0.209

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

-0.55

PromoterAI

0.031

Neutral

(source)

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