rs11596518

chr10-90795254-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HTR7	NM_019859.4	c.540-45660T>C		intron_variant		ENST00000336152.8
HTR7	NM_000872.5	c.540-45660T>C		intron_variant
HTR7	NM_019860.4	c.540-45660T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.540-45660T>C		intron_variant		1	NM_019859.4
HTR7	ENST00000277874.10	c.540-45660T>C		intron_variant		1		A1
HTR7	ENST00000371719.2	c.540-45660T>C		intron_variant		1		P4

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

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.142

Alfa AF: 0.155 Hom.: 326

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11596518; hg19: chr10-92555011;