Genetic Variant ENST00000521530.6:c.1077-25498C>T (chr5-148476770-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000521530.6(HTR4):c.1077-25498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,611,204 control chromosomes in the GnomAD database, including 136,008 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 ( 12347 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123661 hom. )

Consequence

HTR4
ENST00000521530.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

Publications

29 publications found

Variant links:

Genes affected

HTR4 (HGNC:5299): (5-hydroxytryptamine receptor 4) This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]

HTR4 links:

ENSG00000300418 (HGNC:):

ENSG00000300418 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521530.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR4	NM_001040169.2	c.1077-25498C>T	intron	N/A	NP_001035259.1	Q13639-2
HTR4	NM_199453.3	c.1077-10845C>T	intron	N/A	NP_955525.1	Q13639-5
HTR4	NM_001040172.2	c.1077-25C>T	intron	N/A	NP_001035262.2	Q13639-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR4	ENST00000521530.6	TSL:1	c.1077-25498C>T	intron	N/A	ENSP00000428320.1	Q13639-2
HTR4	ENST00000521735.5	TSL:1	c.1077-10845C>T	intron	N/A	ENSP00000430979.1	Q13639-5
HTR4	ENST00000517929.5	TSL:1	c.1077-25C>T	intron	N/A	ENSP00000435904.1	Q13639-3

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59743

AN:

151826

Hom.:

12340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.441

AC:

108052

AN:

245090

AF XY:

0.432

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.407

AC:

593616

AN:

1459260

Hom.:

123661

Cov.:

AF XY:

0.406

AC XY:

294861

AN XY:

725984

show subpopulations

African (AFR)

AF:

0.308

AC:

10293

AN:

33384

American (AMR)

AF:

0.640

AC:

28431

AN:

44428

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

9572

AN:

26084

East Asian (EAS)

AF:

0.558

AC:

22112

AN:

39630

South Asian (SAS)

AF:

0.410

AC:

35190

AN:

85908

European-Finnish (FIN)

AF:

0.394

AC:

21031

AN:

53336

Middle Eastern (MID)

AF:

0.363

AC:

2091

AN:

5758

European-Non Finnish (NFE)

AF:

0.396

AC:

440292

AN:

1110482

Other (OTH)

AF:

0.408

AC:

24604

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

17483

34965

52448

69930

87413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13868

27736

41604

55472

69340

<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:

0.393

AC:

59786

AN:

151944

Hom.:

12347

Cov.:

AF XY:

0.397

AC XY:

29438

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.320

AC:

13238

AN:

41426

American (AMR)

AF:

0.520

AC:

7948

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1265

AN:

3464

East Asian (EAS)

AF:

0.608

AC:

3142

AN:

5168

South Asian (SAS)

AF:

0.412

AC:

1988

AN:

4820

European-Finnish (FIN)

AF:

0.380

AC:

3993

AN:

10514

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.396

AC:

26889

AN:

67966

Other (OTH)

AF:

0.376

AC:

794

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1799

3599

5398

7198

8997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.397

Hom.:

49038

Bravo

AF:

0.404

Asia WGS

AF:

0.517

AC:

1793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.8

(source)

DANN

Benign

0.67

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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