Variant 9-99228061-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.18

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SEC61B	NM_006808.3 linkuse as main transcript	c.203+61A>G		intron_variant		ENST00000223641.5	NP_006799.1	P60468
SEC61B	XM_047422662.1 linkuse as main transcript	c.156+61A>G		intron_variant			XP_047278618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC61B	ENST00000223641.5 linkuse as main transcript	c.203+61A>G		intron_variant		1	NM_006808.3	ENSP00000223641.4		P60468
SEC61B	ENST00000498603.5 linkuse as main transcript	c.41+61A>G		intron_variant		3		ENSP00000474122.1		S4R3B5

Frequencies

GnomAD3 genomes

AF:

0.0615

AC:

9351

AN:

151990

Hom.:

334

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.0623

Gnomad4 ASJ exome

AF:

0.0490

Gnomad4 EAS exome

AF:

0.00964

Gnomad4 SAS exome

AF:

0.0643

Gnomad4 FIN exome

AF:

0.0577

Gnomad4 NFE exome

AF:

0.0780

Gnomad4 OTH exome

AF:

0.0687

GnomAD4 genome

AF:

0.0616

AC:

9369

AN:

152108

Hom.:

335

Cov.:

AF XY:

0.0604

AC XY:

4492

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0395

Gnomad4 AMR

AF:

0.0631

Gnomad4 ASJ

AF:

0.0545

Gnomad4 EAS

AF:

0.0103

Gnomad4 SAS

AF:

0.0597

Gnomad4 FIN

AF:

0.0549

Gnomad4 NFE

AF:

0.0784

Gnomad4 OTH

AF:

0.0636

Alfa

AF:

0.0619

Hom.:

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.36

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over