10-90840482-G-T

Variant names:

• chr10-90840482-G-T
• rs2226116
• NM_019859.4:c.539+16651C>A

Variant summary

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

The NM_019859.4(HTR7):​c.539+16651C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,188 control chromosomes in the GnomAD database, including 1,131 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 0.11 (1131 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.539+16651C>A		intron_variant	Intron 1 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.539+16651C>A		intron_variant	Intron 1 of 2		NP_000863.1
HTR7	NM_019860.4	c.539+16651C>A		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.539+16651C>A		intron_variant	Intron 1 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.539+16651C>A		intron_variant	Intron 1 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.539+16651C>A		intron_variant	Intron 1 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16201 AN: 152070 Hom.: 1132 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.106 AC: 16193 AN: 152188 Hom.: 1131 Cov.: 32 AF XY: 0.104 AC XY: 7770 AN XY: 74396

African (AFR) AF: 0.0268 AC: 1112 AN: 41518

American (AMR) AF: 0.0978 AC: 1496 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.115 AC: 554 AN: 4826

European-Finnish (FIN) AF: 0.115 AC: 1213 AN: 10592

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10802 AN: 67992

Other (OTH) AF: 0.114 AC: 240 AN: 2110

Alfa AF: 0.112 Hom.: 570

Bravo AF: 0.101

Asia WGS AF: 0.0390 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		-0.055
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: rs2226116; hg19: chr10-92600239;