rs11596518

Variant names:

• chr10-90795254-A-G
• rs11596518
• NM_019859.4:c.540-45660T>C

Variant summary

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

The NM_019859.4(HTR7):​c.540-45660T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,208 control chromosomes in the GnomAD database, including 1,874 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 0.14 (1874 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 3 publications found

Genes affected

HTR7 (HGNC:5302): (5-hydroxytryptamine receptor 7) The neurotransmitter, serotonin, is thought to play a role in various cognitive and behavioral functions. The serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors and the gene is a candidate locus for involvement in autistic disorder and other neuropsychiatric disorders. Three splice variants have been identified which encode proteins that differ in the length of their carboxy terminal ends. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.540-45660T>C		intron_variant	Intron 1 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.540-45660T>C		intron_variant	Intron 1 of 2		NP_000863.1
HTR7	NM_019860.4	c.540-45660T>C		intron_variant	Intron 1 of 2		NP_062874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.540-45660T>C		intron_variant	Intron 1 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.540-45660T>C		intron_variant	Intron 1 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.540-45660T>C		intron_variant	Intron 1 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21551 AN: 152090 Hom.: 1873 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.142 AC: 21548 AN: 152208 Hom.: 1874 Cov.: 32 AF XY: 0.143 AC XY: 10638 AN XY: 74410

African (AFR) AF: 0.0345 AC: 1433 AN: 41562

American (AMR) AF: 0.106 AC: 1621 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1022 AN: 5188

South Asian (SAS) AF: 0.128 AC: 618 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2692 AN: 10572

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12941 AN: 67994

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.151 Hom.: 328

Bravo AF: 0.129

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.55
PhyloP100		1.2
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: rs11596518; hg19: chr10-92555011;