rs4792143

Variant names:

• chr17-11482573-C-T
• rs4792143
• NM_207386.4:c.896-69323C>T

Variant summary

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

The NM_207386.4(SHISA6):​c.896-69323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,164 control chromosomes in the GnomAD database, including 2,664 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 0.18 (2664 hom., cov: 33)
• Consequence: SHISA6 NM_207386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA6	NM_207386.4	c.896-69323C>T		intron_variant	Intron 3 of 5	ENST00000441885.8	NP_997269.2
SHISA6	NM_001173462.2	c.896-73167C>T		intron_variant	Intron 3 of 4		NP_001166933.1
SHISA6	NM_001173461.2	c.800-73167C>T		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.896-69323C>T		intron_variant	Intron 3 of 5	5	NM_207386.4	ENSP00000390084.3
SHISA6	ENST00000432116.7	c.896-73167C>T		intron_variant	Intron 3 of 4	1		ENSP00000388659.3
SHISA6	ENST00000409168.7	c.800-73167C>T		intron_variant	Intron 2 of 3	1		ENSP00000387157.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27576 AN: 152048 Hom.: 2663 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.181 AC: 27598 AN: 152164 Hom.: 2664 Cov.: 33 AF XY: 0.182 AC XY: 13537 AN XY: 74404

African (AFR) AF: 0.154 AC: 6389 AN: 41508

American (AMR) AF: 0.234 AC: 3573 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1494 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1564 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11765 AN: 67998

Other (OTH) AF: 0.216 AC: 457 AN: 2112

Alfa AF: 0.187 Hom.: 5160

Bravo AF: 0.189

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.88
PhyloP100		0.21
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: rs4792143; hg19: chr17-11385890;