chr4-118796479-A-G

Variant names:

• chr4-118796479-A-G
• rs10518325
• NM_014822.4:c.1041+1204T>C

Variant summary

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

The NM_001318066.2(SEC24D):​c.1044+1204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,296 control chromosomes in the GnomAD database, including 394 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 0.066 (394 hom., cov: 32)
• Consequence: SEC24D NM_001318066.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 3 publications found

Genes affected

SEC24D (HGNC:10706): (SEC24 homolog D, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC24D Gene-Disease associations (from GenCC):

• Cole-Carpenter syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• Cole-Carpenter syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318066.2. 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
	SEC24D	NM_014822.4	MANE Select	c.1041+1204T>C		intron	N/A	NP_055637.2
	SEC24D	NM_001318066.2		c.1044+1204T>C		intron	N/A	NP_001304995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC24D	ENST00000280551.11	TSL:1 MANE Select	c.1041+1204T>C		intron	N/A	ENSP00000280551.6
	SEC24D	ENST00000509818.5	TSL:1	n.*256+1204T>C		intron	N/A	ENSP00000424085.1
	SEC24D	ENST00000514561.5	TSL:1	n.*1015+1204T>C		intron	N/A	ENSP00000422717.1

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 10008 AN: 152180 Hom.: 396 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0656 AC: 9996 AN: 152296 Hom.: 394 Cov.: 32 AF XY: 0.0655 AC XY: 4879 AN XY: 74466

African (AFR) AF: 0.0313 AC: 1300 AN: 41574

American (AMR) AF: 0.0657 AC: 1005 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3470

East Asian (EAS) AF: 0.0511 AC: 265 AN: 5186

South Asian (SAS) AF: 0.106 AC: 514 AN: 4830

European-Finnish (FIN) AF: 0.0542 AC: 575 AN: 10612

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.0807 AC: 5486 AN: 68014

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0824 Hom.: 1058

Bravo AF: 0.0641

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		0.36
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: rs10518325; hg19: chr4-119717634;