NM_033127.4:c.1546-402C>T

Variant names:

• chr1-177948344-G-A
• rs6695715
• NM_033127.4:c.1546-402C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 3 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.1546-402C>T		intron_variant	Intron 12 of 25	ENST00000308284.11	NP_149118.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30403 AN: 152006 Hom.: 3278 Cov.: 32

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

GnomAD2 exomes AF: 0.228 AC: 33144 AN: 145194 AF XY: 0.229

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 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.: 31 AF XY: 0.222 AC XY: 125000 AN XY: 564236

African (AFR) AF: 0.106 AC: 2592 AN: 24476

American (AMR) AF: 0.214 AC: 6049 AN: 28216

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 4638 AN: 15948

East Asian (EAS) AF: 0.233 AC: 3015 AN: 12966

South Asian (SAS) AF: 0.229 AC: 17395 AN: 75978

European-Finnish (FIN) AF: 0.263 AC: 7157 AN: 27188

Middle Eastern (MID) AF: 0.285 AC: 1258 AN: 4412

European-Non Finnish (NFE) AF: 0.220 AC: 202566 AN: 920588

Other (OTH) AF: 0.221 AC: 9215 AN: 41708

GnomAD4 genome AF: 0.200 AC: 30403 AN: 152124 Hom.: 3275 Cov.: 32 AF XY: 0.203 AC XY: 15087 AN XY: 74354

African (AFR) AF: 0.119 AC: 4951 AN: 41488

American (AMR) AF: 0.220 AC: 3358 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1194 AN: 5174

South Asian (SAS) AF: 0.221 AC: 1069 AN: 4828

European-Finnish (FIN) AF: 0.268 AC: 2833 AN: 10580

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15328 AN: 67982

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.225 Hom.: 3568

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
PhyloP100		-0.087
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6695715; hg19: chr1-177917479; COSMIC: COSV57629882;