5-148645595-C-T

Variant names:

• chr5-148645595-C-T
• rs7713886
• NM_000870.7:c.-48+8467G>A

Variant summary

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

The NM_000870.7(HTR4):​c.-48+8467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,166 control chromosomes in the GnomAD database, including 55,384 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 0.85 (55381 hom., cov: 31)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 3 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]

ENSG00000253297 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.-48+8467G>A		intron_variant	Intron 1 of 6	ENST00000377888.8	NP_000861.1
HTR4	NR_104445.2	n.466+8467G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.-48+8467G>A		intron_variant	Intron 1 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129201 AN: 152042 Hom.: 55326 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.824

GnomAD4 exome AF: 1.00 AC: 6 AN: 6 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 6 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 6 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.850 AC: 129311 AN: 152160 Hom.: 55381 Cov.: 31 AF XY: 0.850 AC XY: 63235 AN XY: 74372

African (AFR) AF: 0.961 AC: 39912 AN: 41524

American (AMR) AF: 0.808 AC: 12352 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2617 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4554 AN: 5176

South Asian (SAS) AF: 0.898 AC: 4324 AN: 4816

European-Finnish (FIN) AF: 0.791 AC: 8349 AN: 10550

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54412 AN: 68018

Other (OTH) AF: 0.827 AC: 1745 AN: 2110

Alfa AF: 0.806 Hom.: 70538

Bravo AF: 0.853

Asia WGS AF: 0.908 AC: 3154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7713886; hg19: chr5-148025158;