Genetic Variant LOC105377864:c.-10895T>A (chr6-77463564-T-A) – 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.-10895T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 673,436 control chromosomes in the GnomAD database, including 26,820 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 ( 5071 hom., cov: 32)

Exomes 𝑓: 0.28 ( 21749 hom. )

Consequence

LOC105377864
XM_047419659.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.677

Publications

79 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=-0.54).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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.-161A>T		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+3336A>T		intron	N/A
	HTR1B	ENST00000369947.5	TSL:6 MANE Select	c.-161A>T		upstream_gene	N/A	ENSP00000358963.3	P28222

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35268

AN:

151876

Hom.:

5069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0703

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.0940

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.278

AC:

145206

AN:

521440

Hom.:

21749

Cov.:

AF XY:

0.278

AC XY:

75293

AN XY:

271252

show subpopulations

African (AFR)

AF:

0.0654

AC:

900

AN:

13756

American (AMR)

AF:

0.296

AC:

5522

AN:

18672

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

4643

AN:

14146

East Asian (EAS)

AF:

0.0732

AC:

2300

AN:

31420

South Asian (SAS)

AF:

0.250

AC:

11635

AN:

46462

European-Finnish (FIN)

AF:

0.361

AC:

10687

AN:

29612

Middle Eastern (MID)

AF:

0.328

AC:

707

AN:

2154

European-Non Finnish (NFE)

AF:

0.300

AC:

100862

AN:

336736

Other (OTH)

AF:

0.279

AC:

7950

AN:

28482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

5394

10788

16182

21576

26970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1254

2508

3762

5016

6270

<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:

0.232

AC:

35280

AN:

151996

Hom.:

5071

Cov.:

AF XY:

0.235

AC XY:

17495

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0702

AC:

2909

AN:

41428

American (AMR)

AF:

0.281

AC:

4298

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1144

AN:

3472

East Asian (EAS)

AF:

0.0934

AC:

481

AN:

5150

South Asian (SAS)

AF:

0.253

AC:

1220

AN:

4814

European-Finnish (FIN)

AF:

0.378

AC:

3992

AN:

10570

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20264

AN:

67952

Other (OTH)

AF:

0.266

AC:

563

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1320

2641

3961

5282

6602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.143

Hom.:

280

Bravo

AF:

0.220

Asia WGS

AF:

0.176

AC:

612

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

-0.68

PromoterAI

-0.044

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