rs17688192

Variant names:

• chr16-20668648-G-A
• rs17688192
• NM_001318890.3:c.912+1179C>T

Variant summary

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

The NM_001318890.3(ACSM1):​c.912+1179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,112 control chromosomes in the GnomAD database, including 3,055 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 0.17 (3055 hom., cov: 32)
• Consequence: ACSM1 NM_001318890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 3 publications found

Genes affected

ACSM1 (HGNC:18049): (acyl-CoA synthetase medium chain family member 1) Enables CoA-ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [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 (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318890.3. 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
	ACSM1	NM_001318890.3	MANE Select	c.912+1179C>T		intron	N/A	NP_001305819.1
	ACSM1	NM_052956.3		c.912+1179C>T		intron	N/A	NP_443188.2
	ACSM1	NR_134918.2		n.1041+1179C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.912+1179C>T		intron	N/A	ENSP00000428047.1
	ACSM1	ENST00000307493.8	TSL:1	c.912+1179C>T		intron	N/A	ENSP00000301956.3
	ACSM1	ENST00000519745.5	TSL:1	n.*358+1179C>T		intron	N/A	ENSP00000428650.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26417 AN: 151994 Hom.: 3056 Cov.: 32

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.174 AC: 26415 AN: 152112 Hom.: 3055 Cov.: 32 AF XY: 0.171 AC XY: 12706 AN XY: 74344

African (AFR) AF: 0.0436 AC: 1810 AN: 41540

American (AMR) AF: 0.205 AC: 3124 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0753 AC: 362 AN: 4810

European-Finnish (FIN) AF: 0.252 AC: 2663 AN: 10562

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17489 AN: 67966

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.226 Hom.: 2340

Bravo AF: 0.164

Asia WGS AF: 0.0480 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.39
PhyloP100		0.038
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: rs17688192; hg19: chr16-20679970;