9-99227663-A-G

Variant names:

• chr9-99227663-A-G
• rs78924437
• NM_006808.3:c.102-236A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006808.3(SEC61B):​c.102-236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,260 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (335 hom., cov: 32)
• Consequence: SEC61B NM_006808.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23
• Publications: 2 publications found

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]

SEC61B Gene-Disease associations (from GenCC):

• polycystic liver disease 1

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• SEC61B-related polycystic liver disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-99227663-A-G is Benign according to our data. Variant chr9-99227663-A-G is described in ClinVar as [Benign]. Clinvar id is 1241775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC61B	NM_006808.3	c.102-236A>G		intron_variant	Intron 2 of 3	ENST00000223641.5	NP_006799.1
SEC61B	XM_047422662.1	c.55-236A>G		intron_variant	Intron 1 of 2		XP_047278618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC61B	ENST00000223641.5	c.102-236A>G		intron_variant	Intron 2 of 3	1	NM_006808.3	ENSP00000223641.4
SEC61B	ENST00000498603.5	c.-61-236A>G		intron_variant	Intron 2 of 3	3		ENSP00000474122.1

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9348 AN: 152142 Hom.: 334 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0615 AC: 9366 AN: 152260 Hom.: 335 Cov.: 32 AF XY: 0.0603 AC XY: 4488 AN XY: 74452

African (AFR) AF: 0.0394 AC: 1636 AN: 41570

American (AMR) AF: 0.0633 AC: 968 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3468

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5184

South Asian (SAS) AF: 0.0592 AC: 286 AN: 4830

European-Finnish (FIN) AF: 0.0547 AC: 579 AN: 10586

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5333 AN: 68000

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0607 Hom.: 46

Bravo AF: 0.0616

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 17, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.73
PhyloP100		-1.2
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: rs78924437; hg19: chr9-101989945; COSMIC: COSV56322313; COSMIC: COSV56322313;