rs9505118

Positions:

• chr6-7290204-A-G

Variant summary

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

The NM_003144.5(SSR1):​c.794-273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,160 control chromosomes in the GnomAD database, including 10,485 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 0.37 (10485 hom., cov: 34)
• Consequence: SSR1 NM_003144.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

SSR1 (HGNC:11323): (signal sequence receptor subunit 1) The signal sequence receptor (SSR) is a glycosylated endoplasmic reticulum (ER) membrane receptor associated with protein translocation across the ER membrane. The SSR consists of 2 subunits, a 34-kD glycoprotein encoded by this gene and a 22-kD glycoprotein. This gene generates several mRNA species as a result of complex alternative polyadenylation. This gene is unusual in that it utilizes arrays of polyA signal sequences that are mostly non-canonical. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSR1	NM_003144.5	c.794-273T>C		intron_variant		ENST00000244763.9
SSR1	NM_001292008.2	c.590-273T>C		intron_variant
SSR1	NR_120448.2	n.794-273T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSR1	ENST00000244763.9	c.794-273T>C		intron_variant		1	NM_003144.5	P4
	ENST00000379928.4	n.212+4308A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56256 AN: 152042 Hom.: 10487 Cov.: 34

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.370 AC: 56279 AN: 152160 Hom.: 10485 Cov.: 34 AF XY: 0.368 AC XY: 27373 AN XY: 74386

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.376

Alfa AF: 0.403 Hom.: 23138

Bravo AF: 0.366

Asia WGS AF: 0.390 AC: 1353 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs9505118; hg19: chr6-7290437;