rs3751501

Variant names:

• chr14-23080076-G-A
• rs3751501
• NM_001386863.1:c.1259C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23080076-G-A
• chr14-23080076-G-C

Variant summary

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

The NM_001386863.1(ACIN1):​c.1259C>T​(p.Ser420Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0542 in 1,614,112 control chromosomes in the GnomAD database, including 2,603 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 0.044 (193 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2410 hom.)
• Consequence: ACIN1 NM_001386863.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 19 publications found

Genes affected

ACIN1 (HGNC:17066): (apoptotic chromatin condensation inducer 1) Apoptosis is defined by several morphologic nuclear changes, including chromatin condensation and nuclear fragmentation. This gene encodes a nuclear protein that induces apoptotic chromatin condensation after activation by caspase-3, without inducing DNA fragmentation. This protein has also been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) that is deposited at splice junctions on mRNAs, as a consequence of pre-mRNA splicing. It may thus be involved in mRNA metabolism associated with splicing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

LOC124903288 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017047822).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACIN1	NM_001386863.1	c.1259C>T	p.Ser420Phe	missense_variant	Exon 6 of 19	ENST00000605057.6	NP_001373792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACIN1	ENST00000605057.6	c.1259C>T	p.Ser420Phe	missense_variant	Exon 6 of 19	1	NM_001386863.1	ENSP00000474349.1
ACIN1	ENST00000262710.5	c.1433C>T	p.Ser478Phe	missense_variant	Exon 6 of 19	1		ENSP00000262710.1
ACIN1	ENST00000555053.5	c.1433C>T	p.Ser478Phe	missense_variant	Exon 6 of 19	1		ENSP00000451328.1
ACIN1	ENST00000457657.5	c.1313C>T	p.Ser438Phe	missense_variant	Exon 5 of 18	5		ENSP00000405677.1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6750 AN: 152124 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0521

GnomAD2 exomes AF: 0.0526 AC: 13216 AN: 251316 AF XY: 0.0522

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.0336

Gnomad NFE exome AF: 0.0602

Gnomad OTH exome AF: 0.0531

GnomAD4 exome AF: 0.0552 AC: 80661 AN: 1461870 Hom.: 2410 Cov.: 63 AF XY: 0.0548 AC XY: 39851 AN XY: 727238

African (AFR) AF: 0.0149 AC: 500 AN: 33480

American (AMR) AF: 0.0374 AC: 1672 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0460 AC: 1203 AN: 26136

East Asian (EAS) AF: 0.112 AC: 4433 AN: 39700

South Asian (SAS) AF: 0.0367 AC: 3165 AN: 86256

European-Finnish (FIN) AF: 0.0344 AC: 1840 AN: 53414

Middle Eastern (MID) AF: 0.0581 AC: 335 AN: 5766

European-Non Finnish (NFE) AF: 0.0577 AC: 64159 AN: 1111998

Other (OTH) AF: 0.0555 AC: 3354 AN: 60396

GnomAD4 genome AF: 0.0443 AC: 6747 AN: 152242 Hom.: 193 Cov.: 32 AF XY: 0.0443 AC XY: 3300 AN XY: 74426

African (AFR) AF: 0.0166 AC: 689 AN: 41546

American (AMR) AF: 0.0406 AC: 621 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.128 AC: 662 AN: 5164

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4830

European-Finnish (FIN) AF: 0.0332 AC: 352 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3896 AN: 68018

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0566 Hom.: 1248

Bravo AF: 0.0438

TwinsUK AF: 0.0612 AC: 227

ALSPAC AF: 0.0599 AC: 231

ESP6500AA AF: 0.0179 AC: 79

ESP6500EA AF: 0.0574 AC: 494

ExAC AF: 0.0535 AC: 6494

Asia WGS AF: 0.0530 AC: 186 AN: 3478

EpiCase AF: 0.0609

EpiControl AF: 0.0598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D;D;D
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.;N
PhyloP100		4.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.98	.;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D
Polyphen		0.98, 0.99	.;D;D;.
Vest4		0.11
MPC		0.13
ClinPred		0.017	T
GERP RS		5.4
Varity_R		0.12
gMVP		0.26
Mutation Taster		=94/6	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: rs3751501; hg19: chr14-23549285; COSMIC: COSV52981529; COSMIC: COSV52981529;