9-99227771-A-G

Variant names:

• chr9-99227771-A-G
• rs17787503
• NM_006808.3:c.102-128A>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.102-128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 654,270 control chromosomes in the GnomAD database, including 1,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (336 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1335 hom.)
• Consequence: SEC61B NM_006808.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.827
• 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=-0.89).
• BP6: Variant 9-99227771-A-G is Benign according to our data. Variant chr9-99227771-A-G is described in ClinVar as [Benign]. Clinvar id is 1183783.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.102-128A>G		intron_variant	Intron 2 of 3	ENST00000223641.5	NP_006799.1
SEC61B	XM_047422662.1	c.55-128A>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.102-128A>G		intron_variant	Intron 2 of 3	1	NM_006808.3	ENSP00000223641.4
SEC61B	ENST00000498603.5	c.-61-128A>G		intron_variant	Intron 2 of 3	3		ENSP00000474122.1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9357 AN: 152150 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0645

GnomAD4 exome AF: 0.0680 AC: 34124 AN: 502002 Hom.: 1335 AF XY: 0.0676 AC XY: 17785 AN XY: 263128

African (AFR) AF: 0.0388 AC: 521 AN: 13426

American (AMR) AF: 0.0648 AC: 1297 AN: 20008

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 707 AN: 14330

East Asian (EAS) AF: 0.00981 AC: 308 AN: 31384

South Asian (SAS) AF: 0.0635 AC: 2826 AN: 44530

European-Finnish (FIN) AF: 0.0560 AC: 1991 AN: 35522

Middle Eastern (MID) AF: 0.0814 AC: 168 AN: 2064

European-Non Finnish (NFE) AF: 0.0780 AC: 24430 AN: 313056

Other (OTH) AF: 0.0678 AC: 1876 AN: 27682

GnomAD4 genome AF: 0.0616 AC: 9375 AN: 152268 Hom.: 336 Cov.: 32 AF XY: 0.0603 AC XY: 4491 AN XY: 74444

African (AFR) AF: 0.0395 AC: 1640 AN: 41560

American (AMR) AF: 0.0633 AC: 968 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3468

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5190

South Asian (SAS) AF: 0.0596 AC: 288 AN: 4830

European-Finnish (FIN) AF: 0.0547 AC: 579 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0784 AC: 5335 AN: 68012

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0609 Hom.: 48

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	-0.89
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		-0.83
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: rs17787503; hg19: chr9-101990053; COSMIC: COSV56322320; COSMIC: COSV56322320;