NM_017640.6:c.2329-2850G>A

Variant names:

• chr6-25548060-G-A
• rs441460
• NM_017640.6:c.2329-2850G>A

Variant summary

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

The NM_017640.6(CARMIL1):​c.2329-2850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,906 control chromosomes in the GnomAD database, including 15,464 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 0.45 (15464 hom., cov: 32)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 26 publications found

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017640.6. 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
	CARMIL1	NM_017640.6	MANE Select	c.2329-2850G>A		intron	N/A	NP_060110.4
	CARMIL1	NM_001173977.2		c.2329-2850G>A		intron	N/A	NP_001167448.1	A0A8V8TRE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.2329-2850G>A		intron	N/A	ENSP00000331983.6	Q5VZK9-1
	CARMIL1	ENST00000865798.1		c.2329-2850G>A		intron	N/A	ENSP00000535857.1
	CARMIL1	ENST00000911480.1		c.2329-2850G>A		intron	N/A	ENSP00000581539.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68061 AN: 151788 Hom.: 15433 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.449 AC: 68141 AN: 151906 Hom.: 15464 Cov.: 32 AF XY: 0.443 AC XY: 32886 AN XY: 74220

African (AFR) AF: 0.484 AC: 20050 AN: 41396

American (AMR) AF: 0.427 AC: 6527 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2524 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2178 AN: 4796

European-Finnish (FIN) AF: 0.355 AC: 3735 AN: 10530

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30396 AN: 67960

Other (OTH) AF: 0.458 AC: 967 AN: 2110

Alfa AF: 0.452 Hom.: 72577

Bravo AF: 0.457

Asia WGS AF: 0.514 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.076
DANN	Benign	0.31
PhyloP100		-1.3
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: rs441460; hg19: chr6-25548288;