Genetic Variant HTR5A:c.-19G>C (chr7-155070881-G-C) – 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.-19G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,584,366 control chromosomes in the GnomAD database, including 111,682 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 0.39 ( 11993 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99689 hom. )

Consequence

HTR5A
NM_024012.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.142

Publications

19 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:

Genome browser will be placed here

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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.-19G>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1	P47898A4D2N2
HTR5A-AS1	NR_038945.1 link	n.524+153C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3 link	c.-19G>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2		P47898

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59790

AN:

151850

Hom.:

11966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.418

AC:

97363

AN:

232648

AF XY:

0.415

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.515

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.369

AC:

527892

AN:

1432398

Hom.:

99689

Cov.:

AF XY:

0.370

AC XY:

263059

AN XY:

710636

show subpopulations

African (AFR)

AF:

0.399

AC:

13261

AN:

33238

American (AMR)

AF:

0.503

AC:

22184

AN:

44142

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

10184

AN:

25186

East Asian (EAS)

AF:

0.481

AC:

18965

AN:

39452

South Asian (SAS)

AF:

0.446

AC:

37449

AN:

84006

European-Finnish (FIN)

AF:

0.467

AC:

18437

AN:

39486

Middle Eastern (MID)

AF:

0.350

AC:

1995

AN:

5696

European-Non Finnish (NFE)

AF:

0.347

AC:

382291

AN:

1101574

Other (OTH)

AF:

0.388

AC:

23126

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

17831

35661

53492

71322

89153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12486

24972

37458

49944

62430

<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:

0.394

AC:

59865

AN:

151968

Hom.:

11993

Cov.:

AF XY:

0.400

AC XY:

29709

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.405

AC:

16764

AN:

41440

American (AMR)

AF:

0.419

AC:

6403

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

1380

AN:

3472

East Asian (EAS)

AF:

0.520

AC:

2674

AN:

5146

South Asian (SAS)

AF:

0.458

AC:

2205

AN:

4818

European-Finnish (FIN)

AF:

0.475

AC:

5010

AN:

10556

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24219

AN:

67948

Other (OTH)

AF:

0.379

AC:

800

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1837

3674

5510

7347

9184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.379

Hom.:

2034

Bravo

AF:

0.394

Asia WGS

AF:

0.512

AC:

1778

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.3

(source)

DANN

Benign

0.82

PhyloP100

0.14

Mutation Taster

=298/2

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