9-99222096-G-C

Position:

• chr9-99222096-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000498603.5(SEC61B):​c.-235G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 678,348 control chromosomes in the GnomAD database, including 1,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (334 hom., cov: 32)
  • Exomes 𝑓: 0.069 (1408 hom.)
• Consequence: SEC61B ENST00000498603.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09

Genes affected

SEC61B (HGNC:16993): (SEC61 translocon subunit beta) The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. This complex consists of three membrane proteins- alpha, beta, and gamma. This gene encodes the beta-subunit protein. The Sec61 subunits are also observed in the post-ER compartment, suggesting that these proteins can escape the ER and recycle back. There is evidence for multiple polyadenylated sites for this transcript. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-99222096-G-C is Benign according to our data. Variant chr9-99222096-G-C is described in ClinVar as [Benign]. Clinvar id is 676239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.99222096G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC61B	ENST00000498603.5	c.-235G>C		5_prime_UTR_variant	1/4	3		ENSP00000474122.1

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8970 AN: 152176 Hom.: 334 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.00924

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0687 AC: 36145 AN: 526054 Hom.: 1408 Cov.: 6 AF XY: 0.0687 AC XY: 18734 AN XY: 272830

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.0626

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.00915

Gnomad4 SAS exome AF: 0.0643

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0790

Gnomad4 OTH exome AF: 0.0660

GnomAD4 genome AF: 0.0589 AC: 8973 AN: 152294 Hom.: 334 Cov.: 32 AF XY: 0.0575 AC XY: 4283 AN XY: 74456

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.0617

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.00926

Gnomad4 SAS AF: 0.0595

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0787

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0116 Hom.: 4

Bravo AF: 0.0585

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.27
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41274648; hg19: chr9-101984378;