rs2969180

Positions:

• chr17-11504584-G-A
• chr17-11504584-G-C

Variant summary

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

The NM_207386.4(SHISA6):​c.896-47312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,960 control chromosomes in the GnomAD database, including 8,987 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 0.34 (8987 hom., cov: 32)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.896-47312G>A		intron_variant		ENST00000441885.8	NP_997269.2
SHISA6	NM_001173461.2	c.800-51156G>A		intron_variant			NP_001166932.1
SHISA6	NM_001173462.2	c.896-51156G>A		intron_variant			NP_001166933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISA6	ENST00000441885.8	c.896-47312G>A		intron_variant		5	NM_207386.4	ENSP00000390084
SHISA6	ENST00000409168.7	c.800-51156G>A		intron_variant		1		ENSP00000387157	P1
SHISA6	ENST00000432116.7	c.896-51156G>A		intron_variant		1		ENSP00000388659

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52255 AN: 151842 Hom.: 8982 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.344 AC: 52278 AN: 151960 Hom.: 8987 Cov.: 32 AF XY: 0.349 AC XY: 25898 AN XY: 74264

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.376

Alfa AF: 0.341 Hom.: 11989

Bravo AF: 0.347

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.34

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: rs2969180; hg19: chr17-11407901; COSMIC: COSV69394072;