rs3995090

Variant names:

• chr5-148466252-A-C
• rs3995090
• ENST00000521530.6:c.1077-14980T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-148466252-A-C
• chr5-148466252-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521530.6(HTR4):​c.1077-14980T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,008 control chromosomes in the GnomAD database, including 12,622 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 0.39 (12622 hom., cov: 32)
• Consequence: HTR4 ENST00000521530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 42 publications found

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]

ENSG00000300418 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_001040169.2	c.1077-14980T>G		intron_variant	Intron 5 of 5		NP_001035259.1
HTR4	NM_199453.3	c.1077-327T>G		intron_variant	Intron 5 of 6		NP_955525.1
LOC107986462	XR_001742935.2	n.344-2668A>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000521530.6	c.1077-14980T>G		intron_variant	Intron 6 of 6	1		ENSP00000428320.1
HTR4	ENST00000521735.5	c.1077-327T>G		intron_variant	Intron 5 of 6	1		ENSP00000430979.1
HTR4	ENST00000522588.5	n.1077-327T>G		intron_variant	Intron 5 of 7	1		ENSP00000430874.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59841 AN: 151890 Hom.: 12617 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.394 AC: 59867 AN: 152008 Hom.: 12622 Cov.: 32 AF XY: 0.398 AC XY: 29594 AN XY: 74276

African (AFR) AF: 0.279 AC: 11571 AN: 41482

American (AMR) AF: 0.526 AC: 8027 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3603 AN: 5168

South Asian (SAS) AF: 0.429 AC: 2064 AN: 4812

European-Finnish (FIN) AF: 0.400 AC: 4219 AN: 10556

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27751 AN: 67954

Other (OTH) AF: 0.385 AC: 813 AN: 2112

Alfa AF: 0.410 Hom.: 46929

Bravo AF: 0.403

Asia WGS AF: 0.553 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.80
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3995090; hg19: chr5-147845815;