chr9-99222654-C-G

Variant names:

• chr9-99222654-C-G
• rs170623
• NM_006808.3:c.101+11C>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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.779
• Publications: 9 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=-0.72).
• 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 rank	MANE	Protein	UniProt
SEC61B	NM_006808.3	c.101+11C>G		intron_variant	Intron 2 of 3	ENST00000223641.5	NP_006799.1
SEC61B	XM_047422662.1	c.-1463C>G		5_prime_UTR_variant	Exon 1 of 3		XP_047278618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC61B	ENST00000223641.5	c.101+11C>G		intron_variant	Intron 2 of 3	1	NM_006808.3	ENSP00000223641.4
SEC61B	ENST00000481573.1	n.161C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
SEC61B	ENST00000498603.5	c.-62+11C>G		intron_variant	Intron 2 of 3	3		ENSP00000474122.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30414 AN: 151922 Hom.: 3841 Cov.: 32

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

GnomAD2 exomes AF: 0.237 AC: 30738 AN: 129562 AF XY: 0.240

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 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.: 28 AF XY: 0.257 AC XY: 172497 AN XY: 670832

African (AFR) AF: 0.0420 AC: 1281 AN: 30524

American (AMR) AF: 0.217 AC: 6836 AN: 31560

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 7531 AN: 23418

East Asian (EAS) AF: 0.0531 AC: 1879 AN: 35374

South Asian (SAS) AF: 0.217 AC: 16475 AN: 76012

European-Finnish (FIN) AF: 0.293 AC: 12800 AN: 43648

Middle Eastern (MID) AF: 0.297 AC: 1652 AN: 5562

European-Non Finnish (NFE) AF: 0.272 AC: 288106 AN: 1060056

Other (OTH) AF: 0.245 AC: 13849 AN: 56504

GnomAD4 genome AF: 0.200 AC: 30418 AN: 152040 Hom.: 3842 Cov.: 32 AF XY: 0.198 AC XY: 14752 AN XY: 74328

African (AFR) AF: 0.0484 AC: 2009 AN: 41498

American (AMR) AF: 0.203 AC: 3101 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3468

East Asian (EAS) AF: 0.0542 AC: 279 AN: 5152

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4816

European-Finnish (FIN) AF: 0.290 AC: 3059 AN: 10562

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19074 AN: 67948

Other (OTH) AF: 0.210 AC: 443 AN: 2112

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 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	-0.72
CADD	Benign	6.9
DANN	Benign	0.82
PhyloP100		-0.78
PromoterAI		-0.0023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs170623; hg19: chr9-101984936; COSMIC: COSV53059949; COSMIC: COSV53059949;