19-38587707-G-C

Position:

• chr19-38587707-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001042600.3(MAP4K1):​c.*41C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,439,774 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (22 hom.)
• Consequence: MAP4K1 NM_001042600.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.185

Genes affected

MAP4K1 (HGNC:6863): (mitogen-activated protein kinase kinase kinase kinase 1) Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

RYR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-38587707-G-C is Benign according to our data. Variant chr19-38587707-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1223674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K1	NM_001042600.3	c.*41C>G		3_prime_UTR_variant	31/31	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6	c.*103C>G		3_prime_UTR_variant	32/32		NP_009112.1
MAP4K1	XM_011526404.2	c.*41C>G		3_prime_UTR_variant	32/32		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857	c.*41C>G		3_prime_UTR_variant	31/31	5	NM_001042600.3	ENSP00000380066.1

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152188 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00247 AC: 613 AN: 248062 Hom.: 4 AF XY: 0.00311 AC XY: 418 AN XY: 134558

Gnomad AFR exome AF: 0.00227

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.00180

Gnomad EAS exome AF: 0.0000555

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.00216

GnomAD4 exome AF: 0.00168 AC: 2167 AN: 1287468 Hom.: 22 Cov.: 19 AF XY: 0.00212 AC XY: 1375 AN XY: 649826

Gnomad4 AFR exome AF: 0.00378

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.0121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000779

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152306 Hom.: 2 Cov.: 31 AF XY: 0.00158 AC XY: 118 AN XY: 74458

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00150 Hom.: 0

Bravo AF: 0.00145

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.66

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: rs113000039; hg19: chr19-39078347;