Genetic Variant NM_000870.7:c.27-17463G>A (chr5-148567725-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000870.7(HTR4):c.27-17463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,968 control chromosomes in the GnomAD database, including 5,094 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 ( 5094 hom., cov: 32)

Consequence

HTR4
NM_000870.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7 link	c.27-17463G>A		intron_variant	Intron 2 of 6	ENST00000377888.8	NP_000861.1	Q13639-1A0A2D3FAF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8 link	c.27-17463G>A		intron_variant	Intron 2 of 6	1	NM_000870.7	ENSP00000367120.4		Q13639-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35709

AN:

151850

Hom.:

5090

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0766

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.235

AC:

35710

AN:

151968

Hom.:

5094

Cov.:

AF XY:

0.231

AC XY:

17180

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0764

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.244

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.324

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.272

Hom.:

790

Bravo

AF:

0.232

Asia WGS

AF:

0.211

AC:

734

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

DANN

Benign

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over