16-20548432-A-G

Variant names:

• chr16-20548432-A-G
• rs141915122
• NM_001105069.2:c.936T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001105069.2(ACSM2B):​c.936T>C​(p.Pro312Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,611,690 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (88 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (68 hom.)
• Consequence: ACSM2B NM_001105069.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0760
• Publications: 0 publications found

Genes affected

ACSM2B (HGNC:30931): (acyl-CoA synthetase medium chain family member 2B) Enables benzoate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-20548432-A-G is Benign according to our data. Variant chr16-20548432-A-G is described in ClinVar as Benign. ClinVar VariationId is 786754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.076 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 88 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105069.2. 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
	ACSM2B	NM_001105069.2	MANE Select	c.936T>C	p.Pro312Pro	synonymous	Exon 7 of 14	NP_001098539.1	Q68CK6
	ACSM2B	NM_182617.4		c.936T>C	p.Pro312Pro	synonymous	Exon 8 of 15	NP_872423.3
	ACSM2B	NM_001410902.1		c.699T>C	p.Pro233Pro	synonymous	Exon 6 of 13	NP_001397831.1	H3BTX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2B	ENST00000329697.10	TSL:1 MANE Select	c.936T>C	p.Pro312Pro	synonymous	Exon 7 of 14	ENSP00000327453.6	Q68CK6
	ACSM2B	ENST00000414188.6	TSL:1	c.936T>C	p.Pro312Pro	synonymous	Exon 6 of 13	ENSP00000390378.3	Q68CK6
	ACSM2B	ENST00000567001.5	TSL:1	c.936T>C	p.Pro312Pro	synonymous	Exon 8 of 15	ENSP00000456378.1	Q68CK6

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3128 AN: 151864 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00236 AC: 592 AN: 250382 AF XY: 0.00206

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.000840

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00191 AC: 2788 AN: 1459710 Hom.: 68 Cov.: 31 AF XY: 0.00205 AC XY: 1490 AN XY: 726102

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0251 AC: 827 AN: 32930

American (AMR) AF: 0.00193 AC: 86 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26120

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39684

South Asian (SAS) AF: 0.00817 AC: 701 AN: 85830

European-Finnish (FIN) AF: 0.00976 AC: 519 AN: 53166

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5756

European-Non Finnish (NFE) AF: 0.000364 AC: 405 AN: 1111298

Other (OTH) AF: 0.00335 AC: 202 AN: 60254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0206 AC: 3134 AN: 151980 Hom.: 88 Cov.: 32 AF XY: 0.0210 AC XY: 1557 AN XY: 74312

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0639 AC: 2639 AN: 41268

American (AMR) AF: 0.00844 AC: 129 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4812

European-Finnish (FIN) AF: 0.0146 AC: 155 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00171 AC: 116 AN: 68022

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00149 Hom.: 1

Bravo AF: 0.0217

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	-0.98
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		0.076
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141915122; hg19: chr16-20559754; COSMIC: COSV100312338; COSMIC: COSV100312338;