rs41272317

Variant names:

• chr3-132618633-C-A
• rs41272317
• NM_032169.5:c.1414+1G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-132618633-C-A
• chr3-132618633-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_032169.5(ACAD11):​c.1414+1G>T variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,579,782 control chromosomes in the GnomAD database, including 526 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (57 hom., cov: 32)
  • Exomes 𝑓: 0.019 (469 hom.)
• Consequence: ACAD11 NM_032169.5 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77
• Publications: 14 publications found

Genes affected

ACAD11 (HGNC:30211): (acyl-CoA dehydrogenase family member 11) This gene encodes an acyl-CoA dehydrogenase enzyme with a preference for carbon chain lengths between 20 and 26. Naturally occurring read-through transcription occurs between the upstream gene NPHP3 (nephronophthisis 3 (adolescent)) and this gene. [provided by RefSeq, Aug 2015]

NPHP3-ACAD11 (HGNC:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACKR4 (HGNC:1611): (atypical chemokine receptor 4) The protein encoded by this gene is a member of the G protein-coupled receptor family, and is a receptor for C-C type chemokines. This receptor has been shown to bind dendritic cell- and T cell-activated chemokines including CCL19/ELC, CCL21/SLC, and CCL25/TECK. A pseudogene of this gene is found on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032169.5. 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
	ACAD11	NM_032169.5	MANE Select	c.1414+1G>T		splice_donor intron	N/A	NP_115545.3
	NPHP3-ACAD11	NR_037804.1		n.5416+1G>T		splice_donor intron	N/A
	ACAD11	NR_132426.2		n.1472+1G>T		splice_donor intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD11	ENST00000264990.11	TSL:1 MANE Select	c.1414+1G>T		splice_donor intron	N/A	ENSP00000264990.6
	ACAD11	ENST00000485198.5	TSL:1	n.1197+8058G>T		intron	N/A	ENSP00000419973.1
	ACAD11	ENST00000481970.2	TSL:5	c.1415G>T	p.Gly472Val	missense	Exon 11 of 11	ENSP00000420907.1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3250 AN: 152034 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00957

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.00605

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0248

GnomAD2 exomes AF: 0.0239 AC: 5353 AN: 224206 AF XY: 0.0262

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.00717

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.0675

Gnomad FIN exome AF: 0.00613

Gnomad NFE exome AF: 0.0144

Gnomad OTH exome AF: 0.0176

GnomAD4 exome AF: 0.0191 AC: 27253 AN: 1427630 Hom.: 469 Cov.: 30 AF XY: 0.0204 AC XY: 14474 AN XY: 709992

African (AFR) AF: 0.0291 AC: 910 AN: 31274

American (AMR) AF: 0.00798 AC: 305 AN: 38212

Ashkenazi Jewish (ASJ) AF: 0.0206 AC: 520 AN: 25216

East Asian (EAS) AF: 0.0441 AC: 1643 AN: 37232

South Asian (SAS) AF: 0.0665 AC: 5328 AN: 80102

European-Finnish (FIN) AF: 0.00655 AC: 346 AN: 52786

Middle Eastern (MID) AF: 0.0209 AC: 118 AN: 5652

European-Non Finnish (NFE) AF: 0.0153 AC: 16799 AN: 1098230

Other (OTH) AF: 0.0218 AC: 1284 AN: 58926

GnomAD4 genome AF: 0.0214 AC: 3257 AN: 152152 Hom.: 57 Cov.: 32 AF XY: 0.0218 AC XY: 1623 AN XY: 74392

African (AFR) AF: 0.0276 AC: 1147 AN: 41506

American (AMR) AF: 0.00949 AC: 145 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3466

East Asian (EAS) AF: 0.0670 AC: 347 AN: 5178

South Asian (SAS) AF: 0.0718 AC: 346 AN: 4818

European-Finnish (FIN) AF: 0.00605 AC: 64 AN: 10578

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1080 AN: 68008

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0181 Hom.: 117

Bravo AF: 0.0210

TwinsUK AF: 0.0138 AC: 51

ALSPAC AF: 0.0187 AC: 72

ESP6500AA AF: 0.0259 AC: 114

ESP6500EA AF: 0.0155 AC: 133

ExAC AF: 0.0255 AC: 3096

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	29
DANN	Uncertain	0.99
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		7.8
ClinPred		0.028	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/100	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		0.91		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.91		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41272317; hg19: chr3-132337477; COSMIC: COSV53894231;