Variant 9-99222654-C-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.101+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,514,698 control chromosomes in the GnomAD database, including 50,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3842 hom., cov: 32)

Exomes 𝑓: 0.26 ( 47143 hom. )

Consequence

SEC61B
NM_006808.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.779

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:

SEC61B (HGNC:):

SEC61B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 9-99222654-C-G is Benign according to our data. Variant chr9-99222654-C-G is described in ClinVar as [Benign]. Clinvar id is 1261657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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.101+11C>G		intron_variant		ENST00000223641.5	NP_006799.1	P60468
SEC61B	XM_047422662.1 linkuse as main transcript	c.-1463C>G		5_prime_UTR_variant	1/3		XP_047278618.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEC61B	ENST00000223641.5 linkuse as main transcript	c.101+11C>G	intron_variant		1	NM_006808.3	ENSP00000223641.4	P60468
SEC61B	ENST00000498603.5 linkuse as main transcript	c.-62+11C>G	intron_variant		3		ENSP00000474122.1	S4R3B5
SEC61B	ENST00000481573.1 linkuse as main transcript	n.161C>G	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30414

AN:

151922

Hom.:

3841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.0538

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.237

AC:

30738

AN:

129562

Hom.:

4033

AF XY:

0.240

AC XY:

16466

AN XY:

68614

show subpopulations

Gnomad AFR exome

AF:

0.0449

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.0585

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.257

AC:

350409

AN:

1362658

Hom.:

47143

Cov.:

AF XY:

0.257

AC XY:

172497

AN XY:

670832

show subpopulations

Gnomad4 AFR exome

AF:

0.0420

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.0531

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.200

AC:

30418

AN:

152040

Hom.:

3842

Cov.:

AF XY:

0.198

AC XY:

14752

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0484

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.0542

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.261

Hom.:

1019

Bravo

AF:

0.188

Asia WGS

AF:

0.123

AC:

427

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 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.9

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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