9-99228061-A-G

Variant names:

• chr9-99228061-A-G
• rs113403897
• NM_006808.3:c.203+61A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006808.3(SEC61B):​c.203+61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,280,222 control chromosomes in the GnomAD database, including 3,631 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)
  • Exomes 𝑓: 0.071 (3296 hom.)
• Consequence: SEC61B NM_006808.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.18
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-99228061-A-G is Benign according to our data. Variant chr9-99228061-A-G is described in ClinVar as [Benign]. Clinvar id is 1233751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC61B	NM_006808.3	c.203+61A>G		intron_variant	Intron 3 of 3	ENST00000223641.5	NP_006799.1
SEC61B	XM_047422662.1	c.156+61A>G		intron_variant	Intron 2 of 2		XP_047278618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC61B	ENST00000223641.5	c.203+61A>G		intron_variant	Intron 3 of 3	1	NM_006808.3	ENSP00000223641.4
SEC61B	ENST00000498603.5	c.41+61A>G		intron_variant	Intron 3 of 3	3		ENSP00000474122.1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9351 AN: 151990 Hom.: 334 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0549

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0643

GnomAD4 exome AF: 0.0715 AC: 80620 AN: 1128114 Hom.: 3296 AF XY: 0.0713 AC XY: 40677 AN XY: 570190

African (AFR) AF: 0.0359 AC: 976 AN: 27166

American (AMR) AF: 0.0623 AC: 2460 AN: 39490

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 1134 AN: 23150

East Asian (EAS) AF: 0.00964 AC: 360 AN: 37342

South Asian (SAS) AF: 0.0643 AC: 4848 AN: 75404

European-Finnish (FIN) AF: 0.0577 AC: 2979 AN: 51654

Middle Eastern (MID) AF: 0.105 AC: 539 AN: 5148

European-Non Finnish (NFE) AF: 0.0780 AC: 63951 AN: 819640

Other (OTH) AF: 0.0687 AC: 3373 AN: 49120

GnomAD4 genome AF: 0.0616 AC: 9369 AN: 152108 Hom.: 335 Cov.: 32 AF XY: 0.0604 AC XY: 4492 AN XY: 74382

African (AFR) AF: 0.0395 AC: 1638 AN: 41496

American (AMR) AF: 0.0631 AC: 965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3470

East Asian (EAS) AF: 0.0103 AC: 53 AN: 5162

South Asian (SAS) AF: 0.0597 AC: 287 AN: 4808

European-Finnish (FIN) AF: 0.0549 AC: 581 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0784 AC: 5332 AN: 67988

Other (OTH) AF: 0.0636 AC: 134 AN: 2106

Alfa AF: 0.0611 Hom.: 48

Bravo AF: 0.0616

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.91
CADD	Benign	0.36
DANN	Benign	0.38
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs113403897; hg19: chr9-101990343; COSMIC: COSV56322327; COSMIC: COSV56322327;