chr16-67187147-A-G

Variant names:

• chr16-67187147-A-G
• rs9924876
• NM_178516.4:c.1041-9T>C

Variant summary

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

The NM_178516.4(EXOC3L1):​c.1041-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 1,612,662 control chromosomes in the GnomAD database, including 772,091 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 0.98 (73629 hom., cov: 31)
  • Exomes 𝑓: 0.98 (698462 hom.)
• Consequence: EXOC3L1 NM_178516.4 intron
• Scores: Splicing: ADA: 0.0006197
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993
• Publications: 9 publications found

Genes affected

EXOC3L1 (HGNC:27540): (exocyst complex component 3 like 1) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization; exocytosis; and peptide hormone secretion. Predicted to be located in secretory granule. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1041-9T>C		intron_variant	Intron 5 of 13	ENST00000314586.11	NP_848611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.1041-9T>C		intron_variant	Intron 5 of 13	2	NM_178516.4	ENSP00000325674.6

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149593 AN: 152134 Hom.: 73574 Cov.: 31

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.973

GnomAD2 exomes AF: 0.983 AC: 246131 AN: 250270 AF XY: 0.983

Gnomad AFR exome AF: 0.996

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.975

Gnomad OTH exome AF: 0.974

GnomAD4 exome AF: 0.978 AC: 1428209 AN: 1460410 Hom.: 698462 Cov.: 62 AF XY: 0.978 AC XY: 710661 AN XY: 726514

African (AFR) AF: 0.996 AC: 33339 AN: 33478

American (AMR) AF: 0.983 AC: 43963 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 25485 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39697 AN: 39698

South Asian (SAS) AF: 0.994 AC: 85705 AN: 86248

European-Finnish (FIN) AF: 0.991 AC: 51706 AN: 52156

Middle Eastern (MID) AF: 0.962 AC: 5551 AN: 5768

European-Non Finnish (NFE) AF: 0.975 AC: 1083780 AN: 1111842

Other (OTH) AF: 0.977 AC: 58983 AN: 60376

GnomAD4 genome AF: 0.983 AC: 149707 AN: 152252 Hom.: 73629 Cov.: 31 AF XY: 0.984 AC XY: 73222 AN XY: 74440

African (AFR) AF: 0.995 AC: 41331 AN: 41528

American (AMR) AF: 0.978 AC: 14965 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3396 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.991 AC: 4788 AN: 4830

European-Finnish (FIN) AF: 0.994 AC: 10554 AN: 10618

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66247 AN: 68008

Other (OTH) AF: 0.973 AC: 2057 AN: 2114

Alfa AF: 0.977 Hom.: 29630

Bravo AF: 0.983

Asia WGS AF: 0.994 AC: 3458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00062
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.030		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: rs9924876; hg19: chr16-67221050;