dbSNP rs6695715: SEC16B:c.1546-402C>T (chr1-177948344-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033127.4(SEC16B):c.1546-402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,303,604 control chromosomes in the GnomAD database, including 31,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3275 hom., cov: 32)

Exomes 𝑓: 0.22 ( 28541 hom. )

Consequence

SEC16B
NM_033127.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Variant links:

Genes affected

SEC16B (HGNC:30301): (SEC16 homolog B, endoplasmic reticulum export factor) SEC16B is a mammalian homolog of S. cerevisiae Sec16 that is required for organization of transitional endoplasmic reticulum (ER) sites and protein export (Bhattacharyya and Glick, 2007 [PubMed 17192411]).[supplied by OMIM, Jun 2009]

SEC16B links:

CRYZL2P-SEC16B (HGNC:53757): (CRYZL2P-SEC16B readthrough) This locus represents naturally occurring read-through transcription between the neighboring CRYZL2P (crystallin zeta like 2 pseudogene) and SEC16B (SEC16 homolog B, endoplasmic reticulum export factor) genes on chromosome 1. The readthrough transcript encodes a protein that shares sequence identity with the downstream gene product. [provided by RefSeq, Oct 2017]

CRYZL2P-SEC16B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC16B	NM_033127.4 link	c.1546-402C>T		intron_variant	Intron 12 of 25	ENST00000308284.11	NP_149118.2	Q96JE7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC16B	ENST00000308284.11 link	c.1546-402C>T		intron_variant	Intron 12 of 25	1	NM_033127.4	ENSP00000308339.6		Q96JE7-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30403

AN:

152006

Hom.:

3278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.228

AC:

33144

AN:

145194

Hom.:

3901

AF XY:

0.229

AC XY:

17934

AN XY:

78410

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.211

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.220

AC:

253885

AN:

1151480

Hom.:

28541

Cov.:

AF XY:

0.222

AC XY:

125000

AN XY:

564236

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.200

AC:

30403

AN:

152124

Hom.:

3275

Cov.:

AF XY:

0.203

AC XY:

15087

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.226

Hom.:

2644

Bravo

AF:

0.191

Asia WGS

AF:

0.210

AC:

731

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.5

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over