4-118783346-T-C

Variant names:

• chr4-118783346-T-C
• rs6828577
• NM_014822.4:c.1041+14337A>G

Variant summary

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

The NM_014822.4(SEC24D):​c.1041+14337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,002 control chromosomes in the GnomAD database, including 31,901 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 0.63 (31901 hom., cov: 31)
• Consequence: SEC24D NM_014822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24D	NM_014822.4	c.1041+14337A>G		intron_variant	Intron 8 of 22	ENST00000280551.11	NP_055637.2
SEC24D	NM_001318066.2	c.1044+14337A>G		intron_variant	Intron 8 of 22		NP_001304995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24D	ENST00000280551.11	c.1041+14337A>G		intron_variant	Intron 8 of 22	1	NM_014822.4	ENSP00000280551.6
SEC24D	ENST00000509818.5	n.*256+14337A>G		intron_variant	Intron 7 of 11	1		ENSP00000424085.1
SEC24D	ENST00000514561.5	n.*1015+14337A>G		intron_variant	Intron 9 of 22	1		ENSP00000422717.1
SEC24D	ENST00000419654.6	c.-292+14337A>G		intron_variant	Intron 8 of 19	5		ENSP00000388324.2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95950 AN: 151884 Hom.: 31868 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.632 AC: 96030 AN: 152002 Hom.: 31901 Cov.: 31 AF XY: 0.638 AC XY: 47427 AN XY: 74298

African (AFR) AF: 0.404 AC: 16718 AN: 41424

American (AMR) AF: 0.695 AC: 10620 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2379 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3189 AN: 5144

South Asian (SAS) AF: 0.721 AC: 3466 AN: 4810

European-Finnish (FIN) AF: 0.798 AC: 8453 AN: 10588

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49244 AN: 67982

Other (OTH) AF: 0.616 AC: 1300 AN: 2112

Alfa AF: 0.697 Hom.: 29791

Bravo AF: 0.612

Asia WGS AF: 0.651 AC: 2264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.9
DANN	Benign	0.55
PhyloP100		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6828577; hg19: chr4-119704501;