Genetic Variant NM_024012.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4 link	c.-102A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1	P47898A4D2N2
HTR5A-AS1	NR_038945.1 link	n.524+236T>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.-102A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2		P47898

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over