rs12249377

Variant names:

• chr10-90833199-C-A
• rs12249377
• NM_019859.4:c.539+23934G>T

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+23934G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,222 control chromosomes in the GnomAD database, including 1,977 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 0.16 (1977 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• Publications: 15 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.539+23934G>T		intron_variant	Intron 1 of 3	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.539+23934G>T		intron_variant	Intron 1 of 2		NP_000863.1
HTR7	NM_019860.4	c.539+23934G>T		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+23934G>T		intron_variant	Intron 1 of 3	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.539+23934G>T		intron_variant	Intron 1 of 2	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.539+23934G>T		intron_variant	Intron 1 of 2	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24485 AN: 152104 Hom.: 1970 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.161 AC: 24512 AN: 152222 Hom.: 1977 Cov.: 32 AF XY: 0.159 AC XY: 11870 AN XY: 74442

African (AFR) AF: 0.175 AC: 7250 AN: 41530

American (AMR) AF: 0.130 AC: 1990 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3470

East Asian (EAS) AF: 0.158 AC: 821 AN: 5180

South Asian (SAS) AF: 0.140 AC: 675 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1613 AN: 10590

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11396 AN: 68010

Other (OTH) AF: 0.136 AC: 287 AN: 2116

Alfa AF: 0.191 Hom.: 1049

Bravo AF: 0.157

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.74
PhyloP100		0.66
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: rs12249377; hg19: chr10-92592956;