rs6822035

Variant names:

• chr4-118789266-A-C
• rs6822035
• NM_014822.4:c.1041+8417T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-118789266-A-C
• chr4-118789266-A-T

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+8417T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,116 control chromosomes in the GnomAD database, including 30,749 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 0.61 (30749 hom., cov: 32)
• Consequence: SEC24D NM_014822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014822.4. 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
	SEC24D	NM_014822.4	MANE Select	c.1041+8417T>G		intron	N/A	NP_055637.2
	SEC24D	NM_001318066.2		c.1044+8417T>G		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+8417T>G		intron	N/A	ENSP00000280551.6
	SEC24D	ENST00000509818.5	TSL:1	n.*256+8417T>G		intron	N/A	ENSP00000424085.1
	SEC24D	ENST00000514561.5	TSL:1	n.*1015+8417T>G		intron	N/A	ENSP00000422717.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92958 AN: 151998 Hom.: 30725 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.612 AC: 93023 AN: 152116 Hom.: 30749 Cov.: 32 AF XY: 0.619 AC XY: 46004 AN XY: 74342

African (AFR) AF: 0.336 AC: 13953 AN: 41488

American (AMR) AF: 0.687 AC: 10495 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2379 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3194 AN: 5166

South Asian (SAS) AF: 0.719 AC: 3465 AN: 4816

European-Finnish (FIN) AF: 0.798 AC: 8449 AN: 10586

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49163 AN: 67988

Other (OTH) AF: 0.597 AC: 1264 AN: 2116

Alfa AF: 0.688 Hom.: 19610

Bravo AF: 0.589

Asia WGS AF: 0.645 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.87
DANN	Benign	0.41
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: rs6822035; hg19: chr4-119710421;