rs2969180

Variant names:

• chr17-11504584-G-A
• rs2969180
• NM_207386.4:c.896-47312G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.896-47312G>A		intron_variant	Intron 3 of 5	ENST00000441885.8	NP_997269.2
SHISA6	NM_001173462.2	c.896-51156G>A		intron_variant	Intron 3 of 4		NP_001166933.1
SHISA6	NM_001173461.2	c.800-51156G>A		intron_variant	Intron 2 of 3		NP_001166932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA6	ENST00000441885.8	c.896-47312G>A		intron_variant	Intron 3 of 5	5	NM_207386.4	ENSP00000390084.3
SHISA6	ENST00000432116.7	c.896-51156G>A		intron_variant	Intron 3 of 4	1		ENSP00000388659.3
SHISA6	ENST00000409168.7	c.800-51156G>A		intron_variant	Intron 2 of 3	1		ENSP00000387157.3

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

African (AFR) AF: 0.342 AC: 14194 AN: 41458

American (AMR) AF: 0.334 AC: 5100 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1059 AN: 3464

East Asian (EAS) AF: 0.511 AC: 2634 AN: 5158

South Asian (SAS) AF: 0.431 AC: 2069 AN: 4800

European-Finnish (FIN) AF: 0.326 AC: 3436 AN: 10550

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22534 AN: 67956

Other (OTH) AF: 0.376 AC: 793 AN: 2108

Alfa AF: 0.341 Hom.: 28573

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
PhyloP100		0.048
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: rs2969180; hg19: chr17-11407901; COSMIC: COSV69394072;