7-133253161-C-T

Variant names:

• chr7-133253161-C-T
• rs73436933
• NM_021807.4:c.60C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BS1 BS2

The NM_021807.4(EXOC4):​c.60C>T​(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,170 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (27 hom.)
• Consequence: EXOC4 NM_021807.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.237
• Publications: 2 publications found

Genes affected

EXOC4 (HGNC:30389): (exocyst complex component 4) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 7-133253161-C-T is Benign according to our data. Variant chr7-133253161-C-T is described in ClinVar as Benign. ClinVar VariationId is 781114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.237 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1571/152318) while in subpopulation AFR AF = 0.0366 (1523/41574). AF 95% confidence interval is 0.0351. There are 36 homozygotes in GnomAd4. There are 729 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021807.4. 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
	EXOC4	NM_021807.4	MANE Select	c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 18	NP_068579.3
	EXOC4	NM_001037126.2		c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 10	NP_001032203.1	Q96A65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 18	ENSP00000253861.4	Q96A65-1
	EXOC4	ENST00000462055.5	TSL:1	n.67C>T		non_coding_transcript_exon	Exon 1 of 9
	EXOC4	ENST00000852803.1		c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 19	ENSP00000522862.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1569 AN: 152200 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00266 AC: 668 AN: 251236 AF XY: 0.00177

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00102 AC: 1494 AN: 1461852 Hom.: 27 Cov.: 30 AF XY: 0.000828 AC XY: 602 AN XY: 727228

African (AFR) AF: 0.0394 AC: 1319 AN: 33476

American (AMR) AF: 0.00107 AC: 48 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111980

Other (OTH) AF: 0.00156 AC: 94 AN: 60392

GnomAD4 genome AF: 0.0103 AC: 1571 AN: 152318 Hom.: 36 Cov.: 32 AF XY: 0.00979 AC XY: 729 AN XY: 74490

African (AFR) AF: 0.0366 AC: 1523 AN: 41574

American (AMR) AF: 0.00261 AC: 40 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00310 Hom.: 2

Bravo AF: 0.0112

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.24
PromoterAI		0.11	Neutral
Mutation Taster		=100/0	polymorphism

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: rs73436933; hg19: chr7-132937917;