rs2328878

Positions:

• chr6-25297457-A-G

Variant summary

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

The NM_017640.6(CARMIL1):​c.138+12548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,990 control chromosomes in the GnomAD database, including 14,179 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 0.42 (14179 hom., cov: 33)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.138+12548A>G		intron_variant		ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.138+12548A>G		intron_variant		1	NM_017640.6	ENSP00000331983	P1
CARMIL1	ENST00000461945.1	c.-112+12548A>G		intron_variant		1		ENSP00000489403
	ENST00000643807.1	n.364+72489T>C		intron_variant, non_coding_transcript_variant
CARMIL1	ENST00000700669.1	c.138+12548A>G		intron_variant				ENSP00000515137

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63552 AN: 151872 Hom.: 14170 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.418 AC: 63584 AN: 151990 Hom.: 14179 Cov.: 33 AF XY: 0.423 AC XY: 31413 AN XY: 74288

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.420

Alfa AF: 0.465 Hom.: 7908

Bravo AF: 0.401

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2328878; hg19: chr6-25297685;