rs880226

Variant names:

• chr6-25402075-A-G
• rs880226
• NM_017640.6:c.139-18039A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-25402075-A-G
• chr6-25402075-A-T

Variant summary

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

The NM_017640.6(CARMIL1):​c.139-18039A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 150,680 control chromosomes in the GnomAD database, including 15,101 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 0.44 (15101 hom., cov: 29)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 9 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]

CMAHP (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	NM_017640.6	MANE Select	c.139-18039A>G		intron	N/A	NP_060110.4
	CARMIL1	NM_001173977.2		c.139-18039A>G		intron	N/A	NP_001167448.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.139-18039A>G		intron	N/A	ENSP00000331983.6
	CARMIL1	ENST00000461945.1	TSL:1	c.-111-18039A>G		intron	N/A	ENSP00000489403.1
	CARMIL1	ENST00000700669.1		c.139-18039A>G		intron	N/A	ENSP00000515137.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 66835 AN: 150564 Hom.: 15082 Cov.: 29

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.444 AC: 66886 AN: 150680 Hom.: 15101 Cov.: 29 AF XY: 0.448 AC XY: 32915 AN XY: 73482

African (AFR) AF: 0.510 AC: 20892 AN: 40938

American (AMR) AF: 0.395 AC: 5993 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1632 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1947 AN: 5112

South Asian (SAS) AF: 0.480 AC: 2281 AN: 4754

European-Finnish (FIN) AF: 0.492 AC: 5015 AN: 10200

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27602 AN: 67760

Other (OTH) AF: 0.439 AC: 918 AN: 2090

Alfa AF: 0.416 Hom.: 12138

Bravo AF: 0.442

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.81
PhyloP100		-0.44
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: rs880226; hg19: chr6-25402303;