chr1-177944384-T-C

Variant names:

• chr1-177944384-T-C
• rs10913469
• NM_033127.4:c.1881+177A>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.1881+177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,072 control chromosomes in the GnomAD database, including 3,990 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 0.22 (3990 hom., cov: 32)
• Consequence: SEC16B NM_033127.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 125 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	NM_033127.4	MANE Select	c.1881+177A>G		intron	N/A	NP_149118.2	Q96JE7-1
	SEC16B	NM_001390834.1		c.1884+177A>G		intron	N/A	NP_001377763.1
	SEC16B	NM_001390835.1		c.1884+177A>G		intron	N/A	NP_001377764.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC16B	ENST00000308284.11	TSL:1 MANE Select	c.1881+177A>G		intron	N/A	ENSP00000308339.6	Q96JE7-1
	SEC16B	ENST00000528461.5	TSL:1	n.*868+177A>G		intron	N/A	ENSP00000475522.1	U3KQ39
	SEC16B	ENST00000870565.1		c.1977+177A>G		intron	N/A	ENSP00000540624.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33377 AN: 151954 Hom.: 3981 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.220 AC: 33420 AN: 152072 Hom.: 3990 Cov.: 32 AF XY: 0.218 AC XY: 16203 AN XY: 74334

African (AFR) AF: 0.304 AC: 12620 AN: 41492

American (AMR) AF: 0.211 AC: 3224 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3466

East Asian (EAS) AF: 0.197 AC: 1013 AN: 5134

South Asian (SAS) AF: 0.178 AC: 857 AN: 4814

European-Finnish (FIN) AF: 0.161 AC: 1711 AN: 10598

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13027 AN: 67982

Other (OTH) AF: 0.200 AC: 423 AN: 2112

Alfa AF: 0.196 Hom.: 9868

Bravo AF: 0.226

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.045
DANN	Benign	0.28
PhyloP100		-1.5
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: rs10913469; hg19: chr1-177913519;