chr5-148476770-G-C

Variant names:

• chr5-148476770-G-C
• rs7733088
• ENST00000521530.6:c.1077-25498C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000521530.6(HTR4):​c.1077-25498C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HTR4 ENST00000521530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 29 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_001040169.2	c.1077-25498C>G		intron_variant	Intron 5 of 5		NP_001035259.1
HTR4	NM_199453.3	c.1077-10845C>G		intron_variant	Intron 5 of 6		NP_955525.1
HTR4	NM_001040172.2	c.1077-25C>G		intron_variant	Intron 5 of 5		NP_001035262.2
LOC107986462	XR_001742935.2	n.441+7753G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000521530.6	c.1077-25498C>G		intron_variant	Intron 6 of 6	1		ENSP00000428320.1
HTR4	ENST00000521735.5	c.1077-10845C>G		intron_variant	Intron 5 of 6	1		ENSP00000430979.1
HTR4	ENST00000517929.5	c.1077-25C>G		intron_variant	Intron 5 of 5	1		ENSP00000435904.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245090 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460594 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726576

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111398

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs7733088; hg19: chr5-147856333;