chr5-148476770-G-A

Variant names:

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

Variant summary

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

The ENST00000521530.6(HTR4):​c.1077-25498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,611,204 control chromosomes in the GnomAD database, including 136,008 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 (12347 hom., cov: 32)
  • Exomes 𝑓: 0.41 (123661 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_001040169.2	c.1077-25498C>T		intron_variant	Intron 5 of 5		NP_001035259.1
HTR4	NM_199453.3	c.1077-10845C>T		intron_variant	Intron 5 of 6		NP_955525.1
HTR4	NM_001040172.2	c.1077-25C>T		intron_variant	Intron 5 of 5		NP_001035262.2
LOC107986462	XR_001742935.2	n.441+7753G>A		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>T		intron_variant	Intron 6 of 6	1		ENSP00000428320.1
HTR4	ENST00000521735.5	c.1077-10845C>T		intron_variant	Intron 5 of 6	1		ENSP00000430979.1
HTR4	ENST00000517929.5	c.1077-25C>T		intron_variant	Intron 5 of 5	1		ENSP00000435904.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59743 AN: 151826 Hom.: 12340 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.441 AC: 108052 AN: 245090 AF XY: 0.432

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.616

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.407 AC: 593616 AN: 1459260 Hom.: 123661 Cov.: 35 AF XY: 0.406 AC XY: 294861 AN XY: 725984

African (AFR) AF: 0.308 AC: 10293 AN: 33384

American (AMR) AF: 0.640 AC: 28431 AN: 44428

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 9572 AN: 26084

East Asian (EAS) AF: 0.558 AC: 22112 AN: 39630

South Asian (SAS) AF: 0.410 AC: 35190 AN: 85908

European-Finnish (FIN) AF: 0.394 AC: 21031 AN: 53336

Middle Eastern (MID) AF: 0.363 AC: 2091 AN: 5758

European-Non Finnish (NFE) AF: 0.396 AC: 440292 AN: 1110482

Other (OTH) AF: 0.408 AC: 24604 AN: 60250

GnomAD4 genome AF: 0.393 AC: 59786 AN: 151944 Hom.: 12347 Cov.: 32 AF XY: 0.397 AC XY: 29438 AN XY: 74238

African (AFR) AF: 0.320 AC: 13238 AN: 41426

American (AMR) AF: 0.520 AC: 7948 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3464

East Asian (EAS) AF: 0.608 AC: 3142 AN: 5168

South Asian (SAS) AF: 0.412 AC: 1988 AN: 4820

European-Finnish (FIN) AF: 0.380 AC: 3993 AN: 10514

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.396 AC: 26889 AN: 67966

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.397 Hom.: 49038

Bravo AF: 0.404

Asia WGS AF: 0.517 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		0.11
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: rs7733088; hg19: chr5-147856333; COSMIC: COSV58795812; COSMIC: COSV58795812;