rs7961991

Variant names:

• chr12-7327532-T-C
• rs7961991
• NM_001080454.2:c.1656+437T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080454.2(ACSM4):​c.1656+437T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,090 control chromosomes in the GnomAD database, including 3,490 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 0.20 (3490 hom., cov: 32)
• Consequence: ACSM4 NM_001080454.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

ACSM4 (HGNC:32016): (acyl-CoA synthetase medium chain family member 4) Predicted to enable decanoate-CoA ligase activity and fatty-acyl-CoA synthase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Predicted to be active in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

CD163L1 (HGNC:30375): (CD163 molecule like 1) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. The SRCR family is defined by a 100-110 amino acid SRCR domain, which may mediate protein-protein interaction and ligand binding. The encoded protein contains twelve SRCR domains, a transmembrane region and a cytoplasmic domain. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSM4	NM_001080454.2	c.1656+437T>C		intron_variant	Intron 12 of 12	ENST00000399422.5	NP_001073923.1
CD163L1	XR_007063067.1	n.4533-600A>G		intron_variant	Intron 20 of 21
CD163L1	XR_007063068.1	n.4533-600A>G		intron_variant	Intron 20 of 22
CD163L1	XR_931282.3	n.4533-600A>G		intron_variant	Intron 20 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSM4	ENST00000399422.5	c.1656+437T>C		intron_variant	Intron 12 of 12	5	NM_001080454.2	ENSP00000382349.4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30698 AN: 151972 Hom.: 3489 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.202 AC: 30724 AN: 152090 Hom.: 3490 Cov.: 32 AF XY: 0.204 AC XY: 15158 AN XY: 74348

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.194

Alfa AF: 0.184 Hom.: 457

Bravo AF: 0.210

Asia WGS AF: 0.181 AC: 632 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs7961991; hg19: chr12-7480128;