Genetic Variant NM_000864.5:c.1080T>C (chr1-23193140-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000864.5(HTR1D):c.1080T>C(p.Asn360Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,054 control chromosomes in the GnomAD database, including 16,786 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 0.14 ( 1917 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14869 hom. )

Consequence

HTR1D
NM_000864.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.508

Publications

21 publications found

Variant links:

Genes affected

HTR1D (HGNC:5289): (5-hydroxytryptamine receptor 1D) Enables G protein-coupled serotonin receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and intestine smooth muscle contraction. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

HTR1D links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=0.508 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1D	NM_000864.5 link	c.1080T>C	p.Asn360Asn	synonymous_variant	Exon 2 of 2	ENST00000374619.2	NP_000855.1	P28221

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2 link	c.1080T>C	p.Asn360Asn	synonymous_variant	Exon 2 of 2	6	NM_000864.5	ENSP00000363748.1		P28221

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21721

AN:

151940

Hom.:

1917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.147

GnomAD2 exomes

AF:

0.165

AC:

41331

AN:

250662

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.0966

Gnomad EAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0738

Gnomad NFE exome

AF:

0.0990

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.125

AC:

182797

AN:

1460996

Hom.:

14869

Cov.:

AF XY:

0.129

AC XY:

94018

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.180

AC:

6009

AN:

33430

American (AMR)

AF:

0.309

AC:

13791

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.0952

AC:

2483

AN:

26094

East Asian (EAS)

AF:

0.213

AC:

8473

AN:

39694

South Asian (SAS)

AF:

0.302

AC:

25995

AN:

86050

European-Finnish (FIN)

AF:

0.0689

AC:

3681

AN:

53412

Middle Eastern (MID)

AF:

0.107

AC:

619

AN:

5764

European-Non Finnish (NFE)

AF:

0.102

AC:

113817

AN:

1111600

Other (OTH)

AF:

0.131

AC:

7929

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

8521

17042

25564

34085

42606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4546

9092

13638

18184

22730

<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:

0.143

AC:

21751

AN:

152058

Hom.:

1917

Cov.:

AF XY:

0.147

AC XY:

10900

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.172

AC:

7125

AN:

41484

American (AMR)

AF:

0.243

AC:

3705

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

319

AN:

3472

East Asian (EAS)

AF:

0.181

AC:

935

AN:

5158

South Asian (SAS)

AF:

0.321

AC:

1544

AN:

4808

European-Finnish (FIN)

AF:

0.0706

AC:

748

AN:

10588

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6900

AN:

68012

Other (OTH)

AF:

0.153

AC:

321

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

890

1780

2671

3561

4451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.119

Hom.:

864

Bravo

AF:

0.155

Asia WGS

AF:

0.274

AC:

951

AN:

3478

EpiCase

AF:

0.0978

EpiControl

AF:

0.0981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.40

(source)

DANN

Benign

0.44

PhyloP100

0.51

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