rs4792139

chr17-11446541-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207386.4(SHISA6):c.895+67032A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,260 control chromosomes in the GnomAD database, including 1,818 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 (1818 hom., cov: 33)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

Genes affected

SHISA6 (HGNC:34491): (shisa family member 6) Predicted to enable ionotropic glutamate receptor binding activity. Predicted to be involved in several processes, including excitatory chemical synaptic transmission; regulation of short-term neuronal synaptic plasticity; and regulation of signal transduction. Predicted to be located in asymmetric, glutamatergic, excitatory synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in glutamatergic synapse; postsynaptic density; and synaptic membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHISA6	NM_207386.4	c.895+67032A>G		intron_variant		ENST00000441885.8
SHISA6	NM_001173461.2	c.800-109199A>G		intron_variant
SHISA6	NM_001173462.2	c.895+67032A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA6	ENST00000441885.8	c.895+67032A>G		intron_variant		5	NM_207386.4
SHISA6	ENST00000409168.7	c.800-109199A>G		intron_variant		1		P1
SHISA6	ENST00000432116.7	c.895+67032A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21690 AN: 152142 Hom.: 1816 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.143 AC: 21704 AN: 152260 Hom.: 1818 Cov.: 33 AF XY: 0.144 AC XY: 10716 AN XY: 74442

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0577

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.133

Alfa AF: 0.122 Hom.: 1692

Bravo AF: 0.143

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	2.7
Dann	Benign	0.86

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: rs4792139; hg19: chr17-11349858;