chr6-7290204-A-G

Variant names:

• chr6-7290204-A-G
• rs9505118
• NM_003144.5:c.794-273T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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]

ENSG00000238221 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SSR1	NM_003144.5	c.794-273T>C		intron_variant	Intron 7 of 7	ENST00000244763.9	NP_003135.2
SSR1	NM_001292008.2	c.590-273T>C		intron_variant	Intron 7 of 7		NP_001278937.1
SSR1	NR_120448.2	n.794-273T>C		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSR1	ENST00000244763.9	c.794-273T>C		intron_variant	Intron 7 of 7	1	NM_003144.5	ENSP00000244763.4

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

African (AFR) AF: 0.304 AC: 12604 AN: 41516

American (AMR) AF: 0.344 AC: 5260 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2165 AN: 5170

South Asian (SAS) AF: 0.431 AC: 2084 AN: 4832

European-Finnish (FIN) AF: 0.364 AC: 3855 AN: 10584

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27691 AN: 67992

Other (OTH) AF: 0.376 AC: 790 AN: 2102

Alfa AF: 0.394 Hom.: 35192

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
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs9505118; hg19: chr6-7290437;