dbSNP rs11568817: LOC105377864:c.-10794A>C (chr6-77463665-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_047419659.1(LOC105377864):c.-10794A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 565,208 control chromosomes in the GnomAD database, including 50,950 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 0.37 ( 11621 hom., cov: 32)

Exomes 𝑓: 0.42 ( 39329 hom. )

Consequence

LOC105377864
XM_047419659.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.174

Publications

51 publications found

Variant links:

Genes affected

LOC105377864 (HGNC:):

LOC105377864 links:

HTR1B (HGNC:5287): (5-hydroxytryptamine receptor 1B) The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

HTR1B 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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369947.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1B	NM_000863.3	MANE Select	c.-262T>G		upstream_gene	N/A	NP_000854.1	P28222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296734	ENST00000741460.1		n.48+3235T>G		intron	N/A
	HTR1B	ENST00000369947.5	TSL:6 MANE Select	c.-262T>G		upstream_gene	N/A	ENSP00000358963.3	P28222

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55967

AN:

151784

Hom.:

11621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.417

GnomAD4 exome

AF:

0.423

AC:

174763

AN:

413304

Hom.:

39329

Cov.:

AF XY:

0.427

AC XY:

92270

AN XY:

216340

show subpopulations

African (AFR)

AF:

0.193

AC:

2278

AN:

11832

American (AMR)

AF:

0.394

AC:

6508

AN:

16516

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

7013

AN:

12956

East Asian (EAS)

AF:

0.104

AC:

3007

AN:

29030

South Asian (SAS)

AF:

0.464

AC:

18237

AN:

39308

European-Finnish (FIN)

AF:

0.463

AC:

12685

AN:

27390

Middle Eastern (MID)

AF:

0.562

AC:

1038

AN:

1846

European-Non Finnish (NFE)

AF:

0.454

AC:

113573

AN:

250148

Other (OTH)

AF:

0.429

AC:

10424

AN:

24278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

4599

9198

13796

18395

22994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.369

AC:

56005

AN:

151904

Hom.:

11621

Cov.:

AF XY:

0.371

AC XY:

27544

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.200

AC:

8287

AN:

41418

American (AMR)

AF:

0.389

AC:

5943

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1855

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

642

AN:

5116

South Asian (SAS)

AF:

0.456

AC:

2191

AN:

4806

European-Finnish (FIN)

AF:

0.482

AC:

5097

AN:

10568

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30546

AN:

67926

Other (OTH)

AF:

0.414

AC:

874

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1724

3448

5173

6897

8621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.403

Hom.:

19069

Bravo

AF:

0.354

Asia WGS

AF:

0.275

AC:

959

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.7

(source)

DANN

Benign

0.64

PhyloP100

-0.17

PromoterAI

0.040

Neutral

(source)

Mutation Taster

=300/0

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