chr5-148484353-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000870.7(HTR4):c.1077-1060T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,612,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
HTR4
NM_000870.7 intron
NM_000870.7 intron
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 0.204
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.017821074).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTR4 | NM_000870.7 | c.1077-1060T>C | intron_variant | ENST00000377888.8 | |||
LOC107986462 | XR_001742935.2 | n.441+15336A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTR4 | ENST00000377888.8 | c.1077-1060T>C | intron_variant | 1 | NM_000870.7 |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152222Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000879 AC: 22AN: 250182Hom.: 0 AF XY: 0.0000961 AC XY: 13AN XY: 135318
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GnomAD4 exome AF: 0.0000288 AC: 42AN: 1460576Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 726652
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GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74490
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ESP6500AA
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2021 | The c.1103T>C (p.I368T) alteration is located in exon 6 (coding exon 6) of the HTR4 gene. This alteration results from a T to C substitution at nucleotide position 1103, causing the isoleucine (I) at amino acid position 368 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at