rs10489882

Variant names:

• chr1-177935360-T-C
• rs10489882
• NM_033127.4:c.2571+938A>G

Variant summary

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

The NM_033127.4(SEC16B):​c.2571+938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,008 control chromosomes in the GnomAD database, including 10,092 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 0.35 (10092 hom., cov: 32)
• Consequence: SEC16B NM_033127.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033127.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	NM_033127.4	MANE Select	c.2571+938A>G		intron	N/A	NP_149118.2
	SEC16B	NM_001390834.1		c.2574+938A>G		intron	N/A	NP_001377763.1
	SEC16B	NM_001390835.1		c.2574+938A>G		intron	N/A	NP_001377764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	ENST00000308284.11	TSL:1 MANE Select	c.2571+938A>G		intron	N/A	ENSP00000308339.6
	SEC16B	ENST00000528461.5	TSL:1	n.*1558+938A>G		intron	N/A	ENSP00000475522.1
	SEC16B	ENST00000327037.8	TSL:2	n.1281+938A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53760 AN: 151890 Hom.: 10092 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53765 AN: 152008 Hom.: 10092 Cov.: 32 AF XY: 0.352 AC XY: 26175 AN XY: 74290

African (AFR) AF: 0.241 AC: 9982 AN: 41452

American (AMR) AF: 0.380 AC: 5803 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1187 AN: 5160

South Asian (SAS) AF: 0.312 AC: 1499 AN: 4812

European-Finnish (FIN) AF: 0.397 AC: 4193 AN: 10556

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.416 AC: 28313 AN: 67984

Other (OTH) AF: 0.408 AC: 860 AN: 2106

Alfa AF: 0.394 Hom.: 24059

Bravo AF: 0.347

Asia WGS AF: 0.271 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		-0.34
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: rs10489882; hg19: chr1-177904495;