dbSNP rs1406946: HTR1E:c.-186+50C>T (chr6-86937873-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000865.3(HTR1E):c.-186+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,710 control chromosomes in the GnomAD database, including 11,555 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 0.36 ( 11496 hom., cov: 32)

Exomes 𝑓: 0.46 ( 59 hom. )

Consequence

HTR1E
NM_000865.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.776

Publications

5 publications found

Variant links:

Genes affected

HTR1E (HGNC:5291): (5-hydroxytryptamine receptor 1E) Enables G protein-coupled serotonin receptor activity and serotonin binding activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

HTR1E links:

ENSG00000301924 (HGNC:):

ENSG00000301924 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1E	NM_000865.3 link	c.-186+50C>T		intron_variant	Intron 1 of 1	ENST00000305344.7	NP_000856.1
HTR1E	XM_011535789.3 link	c.-197C>T		5_prime_UTR_variant	Exon 1 of 2		XP_011534091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1E	ENST00000305344.7 link	c.-186+50C>T		intron_variant	Intron 1 of 1	1	NM_000865.3	ENSP00000307766.4
ENSG00000301924	ENST00000782918.1 link	n.-33G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54474

AN:

152008

Hom.:

11496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.640

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.345

GnomAD4 exome

AF:

0.455

AC:

266

AN:

584

Hom.:

Cov.:

AF XY:

0.475

AC XY:

168

AN XY:

354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.481

AC:

206

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.430

AC:

AN:

128

Other (OTH)

AF:

0.313

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.358

AC:

54475

AN:

152126

Hom.:

11496

Cov.:

AF XY:

0.358

AC XY:

26645

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.139

AC:

5756

AN:

41530

American (AMR)

AF:

0.366

AC:

5598

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1543

AN:

3470

East Asian (EAS)

AF:

0.306

AC:

1580

AN:

5162

South Asian (SAS)

AF:

0.412

AC:

1986

AN:

4822

European-Finnish (FIN)

AF:

0.478

AC:

5050

AN:

10570

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.464

AC:

31536

AN:

67968

Other (OTH)

AF:

0.342

AC:

723

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1638

3276

4914

6552

8190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.423

Hom.:

3404

Bravo

AF:

0.338

Asia WGS

AF:

0.324

AC:

1121

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.9

(source)

DANN

Benign

0.80

PhyloP100

-0.78

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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