dbSNP rs3823534: HTR5A:c.-422A>G (chr7-155070478-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.-422A>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 0.293 in 394,018 control chromosomes in the GnomAD database, including 18,097 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 0.32 ( 8104 hom., cov: 32)

Exomes 𝑓: 0.28 ( 9993 hom. )

Consequence

HTR5A
NM_024012.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

Publications

1 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.-422A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1
HTR5A-AS1	NR_038945.1 link	n.524+556T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3 link	c.-422A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48113

AN:

151922

Hom.:

8076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.298

GnomAD2 exomes

AF:

0.296

AC:

21828

AN:

73852

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.434

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.277

AC:

67109

AN:

241978

Hom.:

9993

Cov.:

AF XY:

0.280

AC XY:

38345

AN XY:

136902

show subpopulations

African (AFR)

AF:

0.431

AC:

2641

AN:

6130

American (AMR)

AF:

0.247

AC:

4090

AN:

16528

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

1749

AN:

6856

East Asian (EAS)

AF:

0.333

AC:

2496

AN:

7498

South Asian (SAS)

AF:

0.329

AC:

16408

AN:

49890

European-Finnish (FIN)

AF:

0.318

AC:

3305

AN:

10402

Middle Eastern (MID)

AF:

0.259

AC:

635

AN:

2452

European-Non Finnish (NFE)

AF:

0.250

AC:

32693

AN:

130998

Other (OTH)

AF:

0.275

AC:

3092

AN:

11224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2178

4355

6533

8710

10888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.317

AC:

48196

AN:

152040

Hom.:

8104

Cov.:

AF XY:

0.318

AC XY:

23621

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.435

AC:

18053

AN:

41474

American (AMR)

AF:

0.266

AC:

4060

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

927

AN:

3466

East Asian (EAS)

AF:

0.349

AC:

1798

AN:

5146

South Asian (SAS)

AF:

0.343

AC:

1654

AN:

4816

European-Finnish (FIN)

AF:

0.311

AC:

3294

AN:

10592

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17396

AN:

67944

Other (OTH)

AF:

0.304

AC:

641

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1670

3339

5009

6678

8348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.299

Hom.:

2583

Bravo

AF:

0.319

Asia WGS

AF:

0.378

AC:

1315

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.0

(source)

DANN

Benign

0.83

PhyloP100

-0.0060

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=300/0

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